Membrane proteins are common

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 that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a

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 ( ...

and can either penetrate the membrane (

transmembrane 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 frequent ...

) or associate with one or the other side of a membrane ( integral monotopic). Peripheral membrane proteins are transiently associated with the cell membrane. Membrane proteins are common, and medically important—about a third of all human proteins are membrane proteins, and these are targets for more than half of all drugs. Nonetheless, compared to other classes of proteins, determining membrane

protein structure Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers specifically polypeptides formed from sequences of amino acids, the monomers of the polymer. A single amino acid monomer ma ...

s remains a challenge in large part due to the difficulty in establishing experimental conditions that can preserve the correct conformation of the protein in isolation from its native environment.

Function

Membrane proteins perform a variety of functions vital to the survival of organisms: *

Membrane receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral m ...

proteins relay signals between the cell's

internal Internal may refer to: *Internality as a concept in behavioural economics *Neijia, internal styles of Chinese martial arts *Neigong or "internal skills", a type of exercise in meditation associated with Daoism *''Internal (album)'' by Safia, 2016 ...

and

external External may refer to: * External (mathematics), a concept in abstract algebra * Externality In economics, an externality or external cost is an indirect cost or benefit to an uninvolved third party that arises as an effect of another party' ...

environments. *

Transport protein A transport protein (variously referred to as a transmembrane pump, transporter, escort protein, acid transport protein, cation transport protein, or anion transport protein) is a protein that serves the function of moving other materials within ...

s move molecules and

ions An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...

across the membrane. They can be categorized according to the Transporter Classification database. * Membrane enzymes may have many activities, such as

oxidoreductase In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. This group of enzymes usually u ...

transferase A transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups (e.g. a methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor). They are involved in hundreds of ...

hydrolase Hydrolase is a class of enzyme that commonly perform as biochemical catalysts that use water to break a chemical bond, which typically results in dividing a larger molecule into smaller molecules. Some common examples of hydrolase enzymes are este ...

. *

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 allow cells to identify each other and interact. For example, proteins involved in

immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

The localization of proteins in membranes can be predicted reliably using hydrophobicity analyses of protein sequences, i.e. the localization of

hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, t ...

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

sequences.

Integral membrane proteins

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 are permanently attached to the membrane. Such proteins can be separated from the biological membranes only using detergents, nonpolar solvents, or sometimes denaturing agents. They can be classified according to their relationship with the

bilayer A bilayer is a double layer of closely packed atoms or molecules. The properties of bilayers are often studied in condensed matter physics, particularly in the context of semiconductor devices, where two distinct materials are united to form jun ...

: * Integral polytopic proteins are transmembrane proteins that span across the membrane more than once. These proteins may have different

transmembrane 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 ...

. These proteins have one of two structural architectures: ** Helix bundle proteins, which are present in all types of

biological membranes A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates the interior of a cell from the external environment or creates intracellular compartments by serving as a boundary between one part of the c ...

; **

Beta barrel In protein structures, a beta barrel is a beta sheet composed of tandem repeats that twists and coils to form a closed toroidal structure in which the first strand is bonded to the last strand (hydrogen bond). Beta-strands in many beta-barrels are ...

proteins, which are found only in outer membranes of

Gram-negative bacteria Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...

, and outer membranes of

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

and

chloroplasts A chloroplast () is a type of membrane-bound organelle known as a plastid that conducts photosynthesis mostly in plant cell, plant and algae, algal cells. The photosynthetic pigment chlorophyll captures the energy from sunlight, converts it, ...

. * Bitopic proteins are transmembrane proteins that span across the membrane only once. Transmembrane helices from these proteins have significantly different amino acid distributions to transmembrane helices from polytopic proteins. *

Integral monotopic protein Integral monotopic proteins are permanently attached to the cell membrane from one side, and are a type of integral membrane protein (IMP). Three-dimensional structures of the following integral monotopic proteins have been determined: *prostagl ...

s are integral membrane proteins that are attached to only one side of the membrane and do not span the whole way across.

Peripheral membrane proteins

Peripheral membrane protein Peripheral membrane proteins, or extrinsic membrane proteins, are membrane proteins that adhere only temporarily to the biological membrane with which they are associated. These proteins attach to integral membrane proteins, or penetrate the perip ...

s are temporarily attached either to 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 ...

or to integral proteins by a combination of

electrostatic Electrostatics is a branch of physics that studies electric charges at rest (static electricity). Since classical times, it has been known that some materials, such as amber, attract lightweight particles after rubbing. The Greek word for amber ...

, and other non-covalent interactions. Peripheral proteins dissociate following treatment with a polar reagent, such as a solution with an elevated pH or high salt concentrations. Integral and peripheral proteins may be post-translationally modified, with added

fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...

diacylglycerol A diglyceride, or diacylglycerol (DAG), is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Two possible forms exist, 1,2-diacylglycerols and 1,3-diacylglycerols. DAGs can act as s ...

prenyl Prenylation (also known as isoprenylation or lipidation) is the addition of hydrophobic molecules to a protein or a biomolecule. It is usually assumed that prenyl groups (3-methylbut-2-en-1-yl) facilitate attachment to cell membranes, similar to ...

chains, or GPI (glycosylphosphatidylinositol), which may be anchored in the lipid bilayer.

Polypeptide toxins

Polypeptide toxins and many antibacterial peptides, such as

colicin A colicin is a type of bacteriocin produced by and toxic to some strains of ''Escherichia coli''. Colicins are released into the environment to reduce competition from other bacterial strains. Colicins bind to outer membrane receptors, using them ...

s or

hemolysin Hemolysins or haemolysins are lipids and proteins that cause lysis of red blood cells by disrupting the cell membrane. Although the lytic activity of some microbe-derived hemolysins on red blood cells may be of great importance for nutrient acqu ...

s, and certain proteins involved in

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

, are sometimes considered a separate category. These proteins are

water-soluble In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solub ...

but can aggregate and associate irreversibly with the lipid bilayer and become reversibly or irreversibly membrane-associated.

In genomes

Membrane proteins, like soluble

globular protein In biochemistry, globular proteins or spheroproteins are spherical ("globe-like") proteins and are one of the common protein types (the others being fibrous, disordered and membrane proteins). Globular proteins are somewhat water-soluble (formi ...

s, fibrous proteins, and

disordered protein In molecular biology, an intrinsically disordered protein (IDP) is a protein that lacks a fixed or ordered protein tertiary structure, three-dimensional structure, typically in the absence of its macromolecular interaction partners, such as other ...

s, are common. It is estimated that 20–30% of all

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s in most

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

s encode for membrane proteins. For instance, about 1000 of the ~4200 proteins of '' E. coli'' are thought to be membrane proteins, 600 of which have been experimentally verified to be membrane resident. In humans, current thinking suggests that fully 30% of the

encodes membrane proteins.

In disease

Membrane proteins are the

targets ''Targets'' is a 1968 American crime thriller film directed by Peter Bogdanovich, produced by Roger Corman, and written by Polly Platt and Bogdanovich, with cinematography by László Kovács.Stephen Jacobs, ''Boris Karloff: More Than a Monster' ...

of over 50% of all modern

medicinal drugs A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhala ...

. Among the human diseases in which membrane proteins have been implicated are

heart disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...

, Alzheimer's and

cystic fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...

Purification of membrane proteins

Although membrane proteins play an important role in all organisms, their purification has historically, and continues to be, a huge challenge for protein scientists. In 2008, 150 unique structures of membrane proteins were available, and by 2019 only 50 human membrane proteins had had their structures elucidated. In contrast, approximately 25% of all proteins are membrane proteins. Their

surfaces make structural and especially functional characterization difficult. Detergents can be used to render membrane proteins

, but these can also alter protein structure and function. Making membrane proteins water-soluble can also be achieved through engineering the protein sequence, replacing selected hydrophobic amino acids with

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are ...

ones, taking great care to maintain secondary structure while revising overall charge.

Affinity chromatography Affinity chromatography is a method of separating a biomolecule from a mixture, based on a highly specific macromolecular binding interaction between the biomolecule and another substance. The specific type of binding interaction depends on the ...

is one of the best solutions for purification of membrane proteins. The activity of membrane proteins decreases very fast in contrast to other proteins. So, affinity chromatography provides a fast and specific purification of membrane proteins. The

polyhistidine-tag A polyhistidine-tag is an amino acid motif in proteins that typically consists of at least six histidine (''His'') residues, often at the N- or C-terminus of the protein. It is also known as hexa histidine-tag, 6xHis-tag, His6 tag, by the US trad ...

is a commonly used tag for membrane protein purification, and the alternative rho1D4 tag has also been successfully used.

References

External links

Organizations

Membrane Protein Structural Dynamics ConsortiumExperts for Membrane Protein Research and Purification

Membrane protein databases

TCDB
- Transporter Classification database, a comprehensive classification of transmembrane transporter proteins
Orientations of Proteins in Membranes (OPM) database
- 3D structures of

integral In mathematics Mathematics is an area of knowledge that includes the topics of numbers, formulas and related structures, shapes and the spaces in which they are contained, and quantities and their changes. These topics are represented i ...

and

peripheral membrane protein Peripheral membrane proteins, or extrinsic membrane proteins, are membrane proteins that adhere only temporarily to the biological membrane with which they are associated. These proteins attach to integral membrane proteins, or penetrate the perip ...

s arranged in the lipid bilayer
Protein Data Bank of Transmembrane Proteins
- 3D models of

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 frequent ...

s approximately arranged in the lipid bilayer.
TransportDB
- Genomics-oriented database of transporters from TIGR
Membrane PDB
- Database of 3D structures of integral membrane proteins and hydrophobic peptides with an emphasis on crystallization conditions
Mpstruc database
- A curated list of selected transmembrane proteins from the

Protein Data Bank The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The data, typically obtained by X-ray crystallography, NMR spectroscopy, or, increasingly, cry ...

MemProtMD
- a database of membrane protein structures simulated by

coarse-grained Granularity (also called graininess), the condition of existing in granules or grains, refers to the extent to which a material or system is composed of distinguishable pieces. It can either refer to the extent to which a larger entity is sub ...

molecular dynamics Molecular dynamics (MD) is a computer simulation method for analyzing the physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a fixed period of time, giving a view of the dynamic "evolution" of the ...

Membranome database Membranome database provides structural and functional information about more than 6000 single-pass (bitopic) transmembrane proteins from ''Homo sapiens'', ''Arabidopsis thaliana'', ''Dictyostelium discoideum'', ''Saccharomyces cerevisiae'', '' ...

provides information about bitopic proteins from several model organisms {{DEFAULTSORT:Membrane Protein