Protein–lipid interaction is the influence of

membrane protein Membrane proteins are common proteins 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 ...

s on the

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids includ ...

physical state In physics, a state of matter is one of the distinct forms in which matter can exist. Four states of matter are observable in everyday life: solid, liquid, gas, and plasma. Many intermediate states are known to exist, such as liquid crystal, ...

or vice versa. The questions which are relevant to understanding of the structure and

function Function or functionality may refer to: Computing * Function key, a type of key on computer keyboards * Function model, a structured representation of processes in a system * Function object or functor or functionoid, a concept of object-oriente ...

of the membrane are: 1) Do intrinsic membrane proteins bind tightly to lipids (see

annular lipid shell Annular lipids (also called shell lipids or boundary lipids) are a set of lipids or lipidic molecules which preferentially bind or stick to the surface of membrane proteins in biological cells. They constitute a layer, or an annulus/ shell, of lipid ...

), and what is the nature of the layer of lipids adjacent to the protein? 2) Do membrane proteins have long-range effects on the order or dynamics of membrane lipids? 3) How do the lipids influence the structure and/or function of membrane proteins? 4) How do

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 which bind to the layer surface interact with lipids and influence their behavior?

Binding of lipids to intrinsic membrane proteins in the bilayer

A large research effort involves approaches to know whether proteins have binding sites which are specific for particular lipids and whether the protein–lipid complexes can be considered to be long-lived, on the order of the time required for the turnover a typical

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

, that is 10⁻³ sec. This is now known through the use of ²H-NMR, ESR, and

fluorescent Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has a longer wavelength, and therefore a lower photon energy, ...

methods. There are two approaches used to measure the relative affinity of lipids binding to specific membrane proteins. These involve the use of lipid analogues in reconstituted phospholipid

vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...

containing the protein of interest: 1) Spin-labeled phospholipids are motionally restricted when they are adjacent to membrane proteins. The result is a component in the ESR spectrum which is broadened. The experimental spectrum can be analyzed as the sum of the two components, a rapidly tumbling species in the "bulk" lipid phase with a sharp spectrum, and a motionally restricted component adjacent to the protein. Membrane protein denaturation causes further broadening of ESR spin label spectrum and throws more light on membrane lipid-proteins interactions 2) Spin-labeled and

brominated Bromine is a chemical element with the symbol Br and atomic number 35. It is the third-lightest element in group 17 of the periodic table (halogens) and is a volatile red-brown liquid at room temperature that evaporates readily to form a simila ...

lipid derivatives are able to quench the intrinsic tryptophan fluorescence from membrane proteins. The efficiency of quenching depends on the distance between the lipid derivative and the fluorescent tryptophans.

Perturbations of the lipid bilayer due to the presence of lateral membrane proteins

Most ²H-NMR experiments with deuterated phospholipids demonstrate that the presence of proteins has little effect on either the order

parameter A parameter (), generally, is any characteristic that can help in defining or classifying a particular system (meaning an event, project, object, situation, etc.). That is, a parameter is an element of a system that is useful, or critical, when ...

of the lipids in the bilayer or the lipid dynamics, as measured by relaxation times. The overall view resulting from NMR experiments is 1) that the exchange rate between boundary and free lipids is rapid, (10⁷ sec⁻¹), 2) that the order parameters of the bound lipid are barely affected by being adjacent to proteins, 3) that the dynamics of the acyl chain reorientations are slowed only slightly in the

frequency Frequency is the number of occurrences of a repeating event per unit of time. It is also occasionally referred to as ''temporal frequency'' for clarity, and is distinct from ''angular frequency''. Frequency is measured in hertz (Hz) which is eq ...

range of 10⁹ sec⁻¹, and 4) that the

orientation Orientation may refer to: Positioning in physical space * Map orientation, the relationship between directions on a map and compass directions * Orientation (housing), the position of a building with respect to the sun, a concept in building de ...

and the dynamics of the polar headgroups are similarly unaffected in any substantial manner by being adjacent to

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. 13C-NMR spectrum also gives information on specific lipid-protein interactions of biomembranes Recent results using non labeled optical methods such as

Dual Polarisation Interferometry Dual-polarization interferometry (DPI) is an analytical technique that probes molecular layers adsorbed to the surface of a waveguide using the evanescent wave of a laser beam. It is used to measure the conformational change in proteins, or othe ...

which measure the birefringence(or order) within lipid bilayers have been used to show how peptide and protein interactions can influence bilayer order, specifically demonstrating the real time association to bilayer and critical peptide concentration after which the peptides penetrate and disrupt the bilayer order.

Backbone and solid chain dynamics of membrane proteins

Solid-state NMR Solid-state NMR (ssNMR) spectroscopy is a technique for characterizing atomic level structure in solid materials e.g. powders, single crystals and amorphous samples and tissues using nuclear magnetic resonance (NMR) spectroscopy. The anisotropic pa ...

techniques have the potential to yield detailed information about the dynamics of individual amino acid residues within a membrane protein. However, the techniques can require large amounts (100–200 mg) of isotopically labeled proteins and are most informative when applied to small proteins where spectroscopic assignments are possible.

Binding of peripheral membrane proteins to the lipid bilayer

Many

s bind to the membrane primarily through interactions with

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 sign ...

s. But there is a diverse group of proteins which interact directly with the surface of 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 ...

. Some, such as

myelin basic protein Myelin basic protein (MBP) is a protein believed to be important in the process of myelination of nerves in the nervous system. The myelin sheath is a multi-layered membrane, unique to the nervous system, that functions as an insulator to greatly ...

, and

spectrin Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. Spectrin forms pentagonal or hexagonal arrangements, forming a scaffold and playing an important role in maintenance of plasma membr ...

have mainly structural roles. A number of

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 ...

proteins can bind to the bilayer surface transiently or under specific conditions. Misfolding processes, typically exposing hydrophobic regions of proteins, often are associated with binding to lipid membranes and subsequent aggregation, for example, during

neurodegenerative disorder A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

s, neuronal stress and apoptosis.

Binding of lipids to intrinsic membrane proteins in the bilayer

Perturbations of the lipid bilayer due to the presence of lateral membrane proteins

Backbone and solid chain dynamics of membrane proteins

Binding of peripheral membrane proteins to the lipid bilayer

See also

References

Further reading