Integral membrane protein
Encyclopedia
An integral membrane protein (IMP) is a protein
molecule
(or assembly of proteins) that is permanently attached to the biological membrane
. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein. Such proteins can be separated from the biological membranes only using detergent
s, nonpolar solvents, or sometimes denaturing
agents.
IMPs comprise a very significant fraction of the proteins encoded in an organism's genome
.
All transmembrane protein
s are IMPs, but not all IMPs are transmembrane proteins.
or nuclear magnetic resonance
spectroscopy
due to the difficulties with extraction and crystallization. In addition, structures of many water-soluble domains of IMPs are available in the Protein Data Bank
. Their membrane-anchoring α-helices have been removed to facilitate the extraction and crystallization.
IMPs can be divided into two groups:
(TM), which spans the entire biological membrane
. Single-pass membrane proteins cross the membrane only once, while multi-pass membrane proteins weave in and out, crossing several times. Single pass TM proteins can be categorized as Type I, which are positioned such that their carboxy-terminus is towards the cytosol, or Type II, which have their amino-terminus towards the cytosol.
, receptors
, enzymes, structural membrane-anchoring domains, proteins involved in accumulation and transduction
of energy, and proteins responsible for cell adhesion
. Classification of transporters can be found in Transporter Classification database.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
(or assembly of proteins) that is permanently attached to the biological membrane
Biological membrane
A biological membrane or biomembrane is an enclosing or separatingmembrane that acts as a selective barrier, within or around a cell. It consists of a lipid bilayer with embedded proteins that may constitute close to 50% of membrane content...
. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein. Such proteins can be separated from the biological membranes only using detergent
Detergent
A detergent is a surfactant or a mixture of surfactants with "cleaning properties in dilute solutions." In common usage, "detergent" refers to alkylbenzenesulfonates, a family of compounds that are similar to soap but are less affected by hard water...
s, nonpolar solvents, or sometimes denaturing
Denaturation (biochemistry)
Denaturation is a process in which proteins or nucleic acids lose their tertiary structure and secondary structure by application of some external stress or compound, such as a strong acid or base, a concentrated inorganic salt, an organic solvent , or heat...
agents.
IMPs comprise a very significant fraction of the proteins encoded in an organism's genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
.
All transmembrane protein
Transmembrane protein
A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
s are IMPs, but not all IMPs are transmembrane proteins.
Structure
Three-dimensional structures of only ~160 different integral membrane proteins are currently determined at atomic resolution by X-ray crystallographyX-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
or nuclear magnetic resonance
Nuclear magnetic resonance
Nuclear magnetic resonance is a physical phenomenon in which magnetic nuclei in a magnetic field absorb and re-emit electromagnetic radiation...
spectroscopy
Spectroscopy
Spectroscopy is the study of the interaction between matter and radiated energy. Historically, spectroscopy originated through the study of visible light dispersed according to its wavelength, e.g., by a prism. Later the concept was expanded greatly to comprise any interaction with radiative...
due to the difficulties with extraction and crystallization. In addition, structures of many water-soluble domains of IMPs are available in the Protein Data Bank
Protein Data Bank
The Protein Data Bank is a repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids....
. Their membrane-anchoring α-helices have been removed to facilitate the extraction and crystallization.
IMPs can be divided into two groups:
- Integral polytopic proteins (Transmembrane proteins)
- Integral monotopic proteinIntegral monotopic proteinIntegral monotopic proteins, are permanently attached to the membrane from one side.Three-dimensional structures of the following integral monotopic proteins have been determined:*prostaglandin H2 syntheses 1 and 2...
s
Integral Polytopic Protein
The most common type of IMP is the transmembrane proteinTransmembrane protein
A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
(TM), which spans the entire biological membrane
Biological membrane
A biological membrane or biomembrane is an enclosing or separatingmembrane that acts as a selective barrier, within or around a cell. It consists of a lipid bilayer with embedded proteins that may constitute close to 50% of membrane content...
. Single-pass membrane proteins cross the membrane only once, while multi-pass membrane proteins weave in and out, crossing several times. Single pass TM proteins can be categorized as Type I, which are positioned such that their carboxy-terminus is towards the cytosol, or Type II, which have their amino-terminus towards the cytosol.
Integral Monotopic Proteins
Integral monotopic proteins, are permanently attached to the membrane from one side. Such domains require detergents for extraction or crystallization, even after removal of their transmembrane helices. Therefore, they are often classified as integral monotopic proteinsDetermination of Protein Structure
The use of hydropathy plots helps determine integral protein structures based on the hydrophobic and hydrophilic characteristics of alpha helical integral proteins.Function
IMPs include transporters, linkers, channelsIon channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
, receptors
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
, enzymes, structural membrane-anchoring domains, proteins involved in accumulation and transduction
Transduction (biophysics)
In biophysics, transduction is the conveyance of energy from one electron to another , at the same time that the class of energy changes.Photonic energy, the kinetic energy of a photon, may follow the following paths:...
of energy, and proteins responsible for cell adhesion
Cell adhesion
Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure...
. Classification of transporters can be found in Transporter Classification database.
Examples
Examples of integral membrane proteins:- Insulin receptorInsulin receptorIn molecular biology, the insulin receptor is a transmembrane receptor that is activated by insulin. It belongs to the large class of tyrosine kinase receptors....
- Some types of cell adhesionCell adhesionCellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure...
proteins or cell adhesion molecules (CAMs) such as IntegrinIntegrinIntegrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....
s, CadherinCadherinCadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...
s, NCAMs, or SelectinSelectinSelectins are a family of cell adhesion molecules . All selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus and calcium-dependent binding...
s. - Some types of receptor proteins
- GlycophorinGlycophorinA Glycophorin is a sialoglycoprotein of the membrane of a red blood cell. It is a membrane-spanning protein and carries sugar molecules. It is heavily glycosylated . Glycophorins are rich in sialic acid, which gives the red cells a very hydrophilic-charged coat...
- RhodopsinRhodopsinRhodopsin, also known as visual purple, is a biological pigment of the retina that is responsible for both the formation of the photoreceptor cells and the first events in the perception of light. Rhodopsins belong to the G-protein coupled receptor family and are extremely sensitive to light,...
- Band 3Band 3Anion Exchanger 1 or Band 3 is a phylogenetically preserved transport protein responsible for mediating the exchange of chloride for bicarbonate across a plasma membrane. Functionally similar members of the AE clade are AE2 and AE3.It is ubiquitous throughout the vertebrates...
- CD36CD36CD36 is an integral membrane protein found on the surface of many cell types in vertebrate animals and is also known as FAT, SCARB3, GP88, glycoprotein IV and glycoprotein IIIb . CD36 is a member of the class B scavenger receptor family of cell surface proteins...
- GPR30GPR30G-protein coupled estrogen receptor 1 also known as the membrane estrogen receptor or G-protein coupled receptor 30 is a G protein-coupled receptor that in humans is encoded by the GPER gene...
See also
- Membrane proteinMembrane proteinA membrane protein is a protein molecule that is attached to, or associated with the membrane of a cell or an organelle. More than half of all proteins interact with membranes.-Function:...
s - Transmembrane proteinTransmembrane proteinA transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
s - Peripheral membrane proteinPeripheral membrane proteinPeripheral membrane proteins are proteins that adhere only temporarily to the biological membrane with which they are associated. These molecules attach to integral membrane proteins, or penetrate the peripheral regions of the lipid bilayer. The regulatory protein subunits of many ion channels and...
s - Orientations of Proteins in Membranes databaseOrientations of Proteins in Membranes databaseOrientations of Proteins in Membranes database provides spatial positions of membrane protein structures with respect to the lipid bilayer. Positions of the proteins are calculated using an implicit solvation model of the lipid bilayer...
- Hydrophilicity plotHydrophilicity plotA hydrophilicity plot is a quantitative analysis of the degree of hydrophobicity or hydrophilicity of amino acids of a protein. It is used to characterize or identify possible structure or domains of a protein....
s
External links
- The Human Membrane Proteome - A comprehensive article covering the transmembrane protein component of the human proteome
- Membrane PDB Database of 3D structures of integral membrane proteins and hydrophobic peptides with emphasis on crystallization conditions
- Membrane proteins of known 3D structure from Stephen White laboratory