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, res ...

s that are part of, or interact with,

biological membrane 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 ...

s. 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 (t ...

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 structures 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 proteins relay signals between the cell's internal and external environments. * Transport proteins move molecules and ions across the membrane. They can be categorized according to the Transporter Classification database. * Membrane

enzymes 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. ...

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 ...

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 o ...

or hydrolase. * Cell adhesion molecules 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 coul ...

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, ...

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 ...

sequences.

Integral membrane proteins

Integral membrane proteins are permanently attached to the membrane. Such proteins can be separated from the biological membranes only using

detergent A detergent is a surfactant or a mixture of surfactants with cleansing properties when in dilute solutions. There are a large variety of detergents, a common family being the alkylbenzene sulfonates, which are soap-like compounds that are m ...

nonpolar solvent A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...

s, 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 junc ...

: *

Integral polytopic 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 are transmembrane proteins that span across the membrane more than once. These proteins may have different transmembrane topology. These proteins have one of two structural architectures: **

Helix bundle A helix bundle is a small protein fold composed of several alpha helices that are usually nearly parallel or antiparallel to each other. Three-helix bundles Three-helix bundles are among the smallest and fastest known cooperatively folding stru ...

proteins, which are present in all types of biological membranes; ** Beta barrel proteins, which are found only in outer membranes of Gram-negative bacteria, and outer membranes of

mitochondria A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...

and chloroplasts. *

Bitopic protein A single-pass membrane protein also known as single-spanning protein or bitopic protein is a transmembrane protein that spans the lipid bilayer only once. These proteins may constitute up to 50% of all transmembrane proteins, depending on the orga ...

s 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 proteins 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 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 ...

, 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, f ...

, diacylglycerol or

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 ...

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

Polypeptide toxins

Polypeptide 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. ...

toxins and many antibacterial peptides, such as colicins 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 acq ...

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 in ...

, 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 (for ...

fibrous proteins In molecular biology, fibrous proteins or scleroproteins are one of the three main classifications of protein structure (alongside globular and membrane proteins). Fibrous proteins are made up of elongated or fibrous polypeptide chains which fo ...

, and

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

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 b ...

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 ...

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 of over 50% of all modern medicinal drugs. 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, h ...

Alzheimer's Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As t ...

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. Ot ...

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 n ...

ones, taking great care to maintain secondary structure while revising overall charge. Affinity chromatography 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 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, an integral assigns numbers to functions in a way that describes displacement, area, volume, and other concepts that arise by combining infinitesimal data. The process of finding integrals is called integration. Along with ...

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, cr ...

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 th ...

* Membranome database provides information about

bitopic protein A single-pass membrane protein also known as single-spanning protein or bitopic protein is a transmembrane protein that spans the lipid bilayer only once. These proteins may constitute up to 50% of all transmembrane proteins, depending on the orga ...

s from several model organisms {{DEFAULTSORT:Membrane Protein