![PDB 1hzx 7TM Sketch Membrane](https://upload.wikimedia.org/wikipedia/commons/f/f5/PDB_1hzx_7TM_Sketch_Membrane.png)
Cell surface receptors (membrane receptors, transmembrane receptors) are
receptors
Receptor may refer to:
*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...
that are embedded in the
plasma membrane of
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
s. They act in
cell signaling
In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
by receiving (binding to)
extracellular molecules. They are specialized
integral membrane protein
An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a signi ...
s that allow communication between the cell and the
extracellular space
Extracellular space refers to the part of a multicellular organism outside the cells, usually taken to be outside the plasma membranes, and occupied by fluid. This is distinguished from intracellular space, which is inside the cells.
The compos ...
. The extracellular molecules may be
hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s,
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
s,
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s,
growth factor
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regul ...
s,
cell adhesion molecule
Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...
s, or
nutrient
A nutrient is a substance used by an organism to survive, grow, and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi, and protists. Nutrients can be incorporated into cells for metabolic purposes or excret ...
s; they react with the receptor to induce changes in the
metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
and activity of a cell. In the process of
signal transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...
,
ligand binding
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a mo ...
affects a
cascading chemical change through the cell membrane.
Structure and mechanism
Many membrane receptors are
transmembrane protein
A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...
s. There are various kinds, including
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
s and
lipoprotein
A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, su ...
s. Hundreds of different receptors are known and many more have yet to be studied.
Transmembrane receptors are typically classified based on their
tertiary
Tertiary ( ) is a widely used but obsolete term for the geologic period from 66 million to 2.6 million years ago.
The period began with the demise of the non-avian dinosaurs in the Cretaceous–Paleogene extinction event, at the start ...
(three-dimensional) structure. If the three-dimensional structure is unknown, they can be classified based on
membrane topology
Topology of a transmembrane protein refers to locations of N- and C-termini of membrane-spanning polypeptide chain with respect to the inner or outer sides of the biological membrane occupied by the protein.
Several databases provide experimenta ...
. In the simplest receptors,
polypeptide chains
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A p ...
cross the
lipid bilayer
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
once, while others, such as the
G-protein coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of protein family, evolution ...
s, cross as many as seven times. Each
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
can have several kinds of membrane receptors, with varying surface distributions. A single receptor may also be differently distributed at different membrane positions, depending on the sort of membrane and cellular function. Receptors are often clustered on the membrane surface, rather than evenly distributed.
Mechanism
Two models have been proposed to explain transmembrane receptors' mechanism of action.
* ''Dimerization'': The dimerization model suggests that prior to ligand binding, receptors exist in a
monomeric
In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization.
Classification
Mo ...
form. When agonist binding occurs, the monomers combine to form an active
dimer
Dimer may refer to:
* Dimer (chemistry), a chemical structure formed from two similar sub-units
** Protein dimer, a protein quaternary structure
** d-dimer
* Dimer model, an item in statistical mechanics, based on ''domino tiling''
* Julius Dimer ...
.
* ''Rotation'': Ligand binding to the extracellular part of the receptor induces a rotation (conformational change) of part of the receptor's transmembrane helices. The rotation alters which parts of the receptor are exposed on the intracellular side of the membrane, altering how the receptor can interact with other proteins within the cell.
Domains
![transmembrane receptor](https://upload.wikimedia.org/wikipedia/commons/4/48/Transmembrane_receptor.svg)
Transmembrane receptors in
plasma membrane can usually be divided into three parts.
Extracellular domains
The extracellular domain is just externally from the cell or
organelle
In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
. If the polypeptide chain crosses the bilayer several times, the external domain comprises loops entwined through the membrane. By definition, a receptor's main function is to recognize and respond to a type of ligand. For example, a
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
,
hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
, or atomic ions may each bind to the extracellular domain as a ligand coupled to receptor.
Klotho is an enzyme which effects a receptor to recognize the ligand (
FGF23
Fibroblast growth factor 23 (FGF23) is a protein and member of the fibroblast growth factor (FGF) family which participates in the regulation of phosphate in plasma and vitamin D metabolism. In humans it is encoded by the gene. FGF23 decreases rea ...
).
Transmembrane domains
Two most abundant classes of transmembrane receptors are
GPCR
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
and
single-pass transmembrane proteins. In some receptors, such as the
nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ne ...
, the transmembrane domain forms a protein pore through the membrane, or around the
ion channel
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
. Upon activation of an extracellular domain by binding of the appropriate ligand, the pore becomes accessible to ions, which then diffuse. In other receptors, the transmembrane domains undergo a conformational change upon binding, which affects intracellular conditions. In some receptors, such as members of the
7TM superfamily, the transmembrane domain includes a ligand binding pocket.
Intracellular domains
The intracellular (or
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
ic) domain of the receptor interacts with the interior of the cell or organelle, relaying the signal. There are two fundamental paths for this interaction:
* The intracellular domain communicates via protein-protein interactions against ''effector proteins'', which in turn pass a signal to the destination.
* With
enzyme-linked receptor An enzyme-linked receptor, also known as a catalytic receptor, is a transmembrane receptor, where the binding of an extracellular ligand causes enzymatic activity on the intracellular side. Hence a catalytic receptor is an integral membrane protei ...
s, the intracellular domain has ''
enzymatic activity
Enzyme assays are laboratory methods for measuring enzymatic activity. They are vital for the study of enzyme kinetics and enzyme inhibition.
Enzyme units
The quantity or concentration of an enzyme can be expressed in molar amounts, as with an ...
''. Often, this is
tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.
Tyrosine kinases belong to a larger cla ...
activity. The enzymatic activity can also be due to an enzyme associated with the intracellular domain.
Signal transduction
Signal transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...
processes through membrane receptors involve the external reactions, in which the ligand binds to a membrane receptor, and the internal reactions, in which intracellular response is triggered.
Signal transduction through membrane receptors requires four parts:
* Extracellular signaling molecule: an extracellular signaling molecule is produced by one cell and is at least capable of traveling to neighboring cells.
* Receptor protein: cells must have cell surface receptor proteins which bind to the signaling molecule and communicate inward into the cell.
* Intracellular signaling proteins: these pass the signal to the organelles of the cell. Binding of the signal molecule to the receptor protein will activate intracellular signaling proteins that initiate a signaling cascade.
* Target proteins: the conformations or other properties of the target proteins are altered when a signaling pathway is active and changes the behavior of the cell.
![Three conformation states of acetylcholine receptor](https://upload.wikimedia.org/wikipedia/commons/9/91/Three_conformation_states_of_acetylcholine_receptor.jpg)
Membrane receptors are mainly divided by structure and function into 3 classes: The
ion channel linked receptor; The
enzyme-linked receptor An enzyme-linked receptor, also known as a catalytic receptor, is a transmembrane receptor, where the binding of an extracellular ligand causes enzymatic activity on the intracellular side. Hence a catalytic receptor is an integral membrane protei ...
; and The
G protein-coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
.
*Ion channel linked receptors have ion channels for anions and cations, and constitute a large family of multipass transmembrane proteins. They participate in rapid signaling events usually found in electrically active cells such as
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s. They are also called
ligand-gated ion channel
Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...
s. Opening and closing of ion channels is controlled by
neurotransmitters
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neur ...
.
*Enzyme-linked receptors are either enzymes themselves, or directly activate associated enzymes. These are typically single-pass transmembrane receptors, with the enzymatic component of the receptor kept intracellular. The majority of enzyme-linked receptors are, or associate with, protein kinases.
*G protein-coupled receptors are integral membrane proteins that possess seven transmembrane helices. These receptors activate a
G protein
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their act ...
upon
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
binding, and the G-protein mediates receptor effects on intracellular signaling pathways.
Ion channel-linked receptor
During the signal transduction event in a neuron, the neurotransmitter binds to the receptor and alters the conformation of the protein. This opens the ion channel, allowing extracellular ions into the cell. Ion permeability of the plasma membrane is altered, and this transforms the extracellular chemical signal into an intracellular electric signal which alters the
cell excitability
Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charges ...
.
The
acetylcholine receptor
An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.
Classification
Like other transmembrane receptors, acetylcholine receptors are classified according ...
is a receptor linked to a cation channel. The protein consists of four subunits: alpha (α), beta (β), gamma (γ), and delta (δ) subunits. There are two α subunits, with one
acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
binding site each. This receptor can exist in three conformations. The closed and unoccupied state is the native protein conformation. As two molecules of acetylcholine both bind to the binding sites on α subunits, the conformation of the receptor is altered and the gate is opened, allowing for the entry of many ions and small molecules. However, this open and occupied state only lasts for a minor duration and then the gate is closed, becoming the closed and occupied state. The two molecules of acetylcholine will soon dissociate from the receptor, returning it to the native closed and unoccupied state.
Enzyme-linked receptors
![Structure of IGF-1R](https://upload.wikimedia.org/wikipedia/commons/1/17/Structure_of_IGF-1R.jpg)
As of 2009, there are 6 known types of
enzyme-linked receptor An enzyme-linked receptor, also known as a catalytic receptor, is a transmembrane receptor, where the binding of an extracellular ligand causes enzymatic activity on the intracellular side. Hence a catalytic receptor is an integral membrane protei ...
s: Receptor
tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.
Tyrosine kinases belong to a larger cla ...
s; Tyrosine kinase associated receptors; Receptor-like
tyrosine phosphatases; Receptor
serine/
threonine
Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COO ...
kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
s; Receptor
guanylyl cyclase
Guanylate cyclase (EC 4.6.1.2, also known as guanyl cyclase, guanylyl cyclase, or GC; systematic name GTP diphosphate-lyase (cyclizing; 3′,5′-cyclic-GMP-forming)) is a lyase enzyme that converts guanosine triphosphate (GTP) to cyclic guanos ...
s and
histidine kinase
Histidine kinases (HK) are multifunctional, and in non-animal kingdoms, typically transmembrane, proteins of the transferase class of enzymes that play a role in signal transduction across the cellular membrane. The vast majority of HKs are hom ...
associated receptors. Receptor tyrosine kinases have the largest population and widest application. The majority of these molecules are receptors for
growth factor
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regul ...
s such as
epidermal growth factor (EGF),
platelet-derived growth factor
Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing blood v ...
(PDGF),
fibroblast growth factor
Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their ...
(FGF),
hepatocyte growth factor
Hepatocyte growth factor (HGF) or scatter factor (SF) is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts on ...
(HGF),
nerve growth factor (NGF) and
hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s such as
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
.
Most of these receptors will dimerize after binding with their ligands, in order to activate further signal transductions. For example, after the
epidermal growth factor (EGF) receptor binds with its ligand EGF, the two receptors dimerize and then undergo
phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
of the
tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...
residues in the enzyme portion of each receptor molecule. This will activate the tyrosine kinase and catalyze further intracellular reactions.
G protein-coupled receptors
G protein-coupled receptors comprise a large
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
family of transmembrane receptors. They are found only in
eukaryote
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
s.
The
ligands
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electro ...
which bind and activate these receptors include: photosensitive compounds,
odor
An odor (American English) or odour (English in the Commonwealth of Nations, Commonwealth English; American and British English spelling differences#-our, -or, see spelling differences) is caused by one or more volatilized chemical compounds ...
s,
pheromone
A pheromone () is a secreted or excreted chemical factor that triggers a social response in members of the same species. Pheromones are chemicals capable of acting like hormones outside the body of the secreting individual, to affect the behavio ...
s,
hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s, and
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
s. These vary in size from small molecules to
peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A ...
s and large
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s. G protein-coupled receptors are involved in many diseases, and thus are the targets of many modern medicinal drugs.
There are two principal signal transduction pathways involving the G-protein coupled receptors: the
cAMP
Camp may refer to:
Outdoor accommodation and recreation
* Campsite or campground, a recreational outdoor sleeping and eating site
* a temporary settlement for nomads
* Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...
signaling pathway and the
phosphatidylinositol
Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...
signaling pathway. Both are mediated via
G protein
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their act ...
activation. The G-protein is a trimeric protein, with three subunits designated as α, β, and γ. In response to receptor activation, the α subunit releases bound
guanosine diphosphate
Guanosine diphosphate, abbreviated GDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside guanosine. GDP consists of a pyrophosphate group, a pentose sugar ribose, and the nucleobase guanine.
GDP is the product ...
(GDP), which is displaced by
guanosine triphosphate
Guanosine-5'-triphosphate (GTP) is a purine nucleoside triphosphate. It is one of the building blocks needed for the synthesis of RNA during the transcription process. Its structure is similar to that of the guanosine nucleoside, the only d ...
(GTP), thus activating the α subunit, which then dissociates from the β and γ subunits. The activated α subunit can further affect intracellular signaling proteins or target functional proteins directly.
Membrane receptor-related disease
If the membrane receptors are denatured or deficient, the signal transduction can be hindered and cause diseases. Some diseases are caused by disorders of membrane receptor function. This is due to deficiency or degradation of the receptor via changes in the genes that encode and regulate the receptor protein. The membrane receptor
TM4SF5 influences the migration of hepatic cells and
hepatoma
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.
It occurs in t ...
. Also, the cortical NMDA receptor influences membrane fluidity, and is altered in Alzheimer's disease. When the cell is infected by a non-enveloped virus, the virus first binds to specific membrane receptors and then passes itself or a subviral component to the cytoplasmic side of the cellular membrane. In the case of
poliovirus
A poliovirus, the causative agent of polio (also known as poliomyelitis), is a serotype of the species ''Enterovirus C'', in the family of ''Picornaviridae''. There are three poliovirus serotypes: types 1, 2, and 3.
Poliovirus is composed of an ...
, it is known in vitro that interactions with receptors cause conformational rearrangements which release a virion protein called VP4.The N terminus of VP4 is myristylated and thus hydrophobic【
myristic acid
Myristic acid (IUPAC name: tetradecanoic acid) is a common saturated fatty acid with the molecular formula CH3(CH2)12COOH. Its salts and esters are commonly referred to as myristates or tetradecanoates. It is named after the binomial name for nut ...
=CH
3(CH
2)
12COOH】. It is proposed that the conformational changes induced by receptor binding result in the attachment of myristic acid on VP4 and the formation of a channel for RNA.
Structure-based drug design
![Flow charts of two strategies of structure based drug design](https://upload.wikimedia.org/wikipedia/commons/b/b8/Flow_charts_of_two_strategies_of_structure_based_drug_design.jpg)
Through methods such as
X-ray crystallography
X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
and
NMR spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fiel ...
, the information about 3D structures of target molecules has increased dramatically, and so has structural information about the ligands. This drives rapid development of
structure-based drug design. Some of these new drugs target membrane receptors. Current approaches to structure-based drug design can be divided into two categories. The first category is about determining ligands for a given receptor. This is usually accomplished through database queries, biophysical simulations, and the construction of chemical libraries. In each case, a large number of potential ligand molecules are screened to find those fitting the binding pocket of the receptor. This approach is usually referred to as ligand-based drug design. The key advantage of searching a database is that it saves time and power to obtain new effective compounds. Another approach of structure-based drug design is about combinatorially mapping ligands, which is referred to as receptor-based drug design. In this case, ligand molecules are engineered within the constraints of a binding pocket by assembling small pieces in a stepwise manner. These pieces can be either atoms or molecules. The key advantage of such a method is that novel structures can be discovered.
Other examples
*
Adrenergic receptor
*
Olfactory receptor
Olfactory receptors (ORs), also known as odorant receptors, are chemoreceptors expressed in the cell membranes of olfactory receptor neurons and are responsible for the detection of odorants (for example, compounds that have an odor) which give r ...
s
*
Receptor tyrosine kinase
Receptor tyrosine kinases (RTKs) are the high- affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kin ...
s
*
Epidermal growth factor receptor
The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands.
The epidermal growth factor recept ...
*
Insulin Receptor
The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of receptor tyrosine kinase. Metabolically, the insulin receptor plays a key role in the regulation of glucose ho ...
*
Fibroblast growth factor receptors,
*
High affinity neurotrophin receptors
*
Ephrin receptor
Eph receptors (Ephs, after erythropoietin-producing human hepatocellular receptors) are a group of receptors that are activated in response to binding with Eph receptor-interacting proteins (Ephrins). Ephs form the largest known subfamily of rec ...
s
*
Integrins
Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...
*
Low Affinity Nerve Growth Factor Receptor
The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. p75NTR is a neurotrophic facto ...
*
NMDA receptor
* Several
Immune receptors
An immune receptor (or immunologic receptor) is a receptor, usually on a cell membrane, which binds to a substance (for example, a cytokine) and causes a response in the immune system.
Types
The main receptors in the immune system are pattern ...
**
Toll-like receptor
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are Bitopic protein, single-pass membrane-spanning Receptor (biochemistry), receptors usually expressed on sentinel cells such as macrophage ...
**
T cell receptor
The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding b ...
**
CD28
CD28 (Cluster of Differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival. T cell stimulation through CD28 in addition to the T-cell receptor ( TCR) can provid ...
**
SCIMP protein
See also
*
Second messenger
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form or cell signaling, encompassing both first me ...
*
Neuromodulators
Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second ...
References
External links
IUPHAR GPCR Database*
{{Authority control
Transmembrane receptors
Cell signaling
de:Rezeptor#Membranrezeptoren