A
membrane protein is a
proteinProteins 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 that is attached to, or associated with the membrane of a
cellThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
or an
organelleIn cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....
. More than half of all proteins interact with membranes.
Function
Biological membraneA 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...
s consist of a
phospholipidPhospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
bilayerThe lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...
and a variety of proteins that accomplish vital biological functions.
- Structural proteins are attached to microfilament
Microfilaments are the thinnest filaments of the cytoskeleton, a structure found in the cytoplasm of all eukaryotic cells. These linear polymers of actin subunits are flexible and relatively strong, resisting buckling by multi-piconewton compressive forces and filament fracture by nanonewton...
s in the cytoskeletonThe cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
which ensures stability of the cell.
- Cell adhesion molecule
Cell Adhesion Molecules are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix in the process called cell adhesion....
s allow cells to identify each other and interact. Such proteins are involved in immune response, for example.
- Membrane enzymes produce a variety of substances essential for cell function.
- Membrane receptor
Cell surface receptors are specialized integral membrane proteins that take part in communication between the cell and the outside world...
proteins serve as connection between the cell's internalThe cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
and external environments.
- Transport proteins play an important role in the maintenance of concentrations of ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
s. These transport proteins come in two forms: carrier proteinCarrier proteins are proteins involved in the movement of ions, small molecules, or macromolecules, such as another protein, across a biological membrane. Carrier proteins are integral membrane proteins; that is they exist within and span the membrane across which they transport substances. The...
s and channel proteins.
- [ [membrane cells]] are the is a biological membrane that separates the interior of all cells from the outside environment
Main categories
Membrane proteins can be divided into several categories:
- Integral membrane proteins which are permanently bound to the lipid bilayer
The lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...
- Peripheral membrane proteins that are temporarily associated with lipid bilayer or with integral membrane proteins
- Lipid-anchored proteins bound to lipid bilayer bound through lipidated amino acid residues
In addition, pore-forming toxins and many antibacterial peptides are water-soluble molecules, but undergo a conformational transition upon association with lipid bilayer and become reversibly or irreversibly membrane-associated.
A slightly different classification is to divide all membrane proteins to integral and
amphitropic. The amphitropic are proteins that can exist in two alternative states: a water-soluble and a lipid bilayer-bound. The amphitropic protein category includes water-soluble channel-forming polypeptide toxins, which associate irreversibly with membranes, but excludes peripheral proteins that interact with other membrane proteins rather than with lipid bilayer.
Integral membrane proteins
Integral membrane proteinAn integral membrane protein is a protein molecule 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...
s are permanently attached to the membrane. They can be defined as those proteins which require a
detergentA 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...
(such as
SDSSodium dodecyl sulfate , sodium laurilsulfate or sodium lauryl sulfate is an organic compound with the formula CH311OSO3Na). It is an anionic surfactant used in many cleaning and hygiene products...
or Triton X-100) or some other apolar solvent to be displaced. They can be classified according to their relationship with the bilayer:
- Integral polytopic proteins, also known as "transmembrane proteins," are proteins that are permanently attached to the lipid membrane and span across the membrane (at least once). The transmembrane regions of the proteins are either beta-barrels or alpha-helical
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
. The alpha-helical domains are present in all types of biological membranes including outer membraneThe bacterial outer membrane is found in Gram-negative bacteria. Its composition is distinct from that of the cytoplasmic membrane - among other things, the outer leaflet of the membrane includes a complex lipopolysaccharide whose lipid portion acts as an endotoxin - and it is linked to the cell's...
s. The beta-barrels were found only in outer membranes of Gram-negative bacteria, lipid-rich cell walls of a few Gram-positive bacteria, and outer membranes of mitochondria and chloroplasts.
- Integral monotopic protein
Integral 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 are proteins that are permanently attached to the lipid membrane from only one side and do not span across the membrane.
Peripheral membrane proteins
Peripheral membrane proteins are also known as extrinsic proteins, they do not interact with the hydrophobic core of the lipid bilayer. Some peripheral membrane proteins are located at the outer part of the plasma membrane (exoplasmic). They interact with the membrane indirectly by binding to the integral membrane proteins.
Peripheral 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 are temporarily attached either to the
lipid bilayerThe lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...
or to integral proteins by a combination of hydrophobic, electrostatic, and other non-covalent interactions. Peripheral proteins dissociate following treatment with a polar reagent, such as a solution with an elevated
pHIn chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
or high salt concentrations.
Integral and peripheral proteins may be post-translationally modified, with added
fatty acidIn chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
or prenyl chains, or
GPIGlycosylphosphatidylinositol is a glycolipid that can be attached to the C-terminus of a protein during posttranslational modification...
(glycosylphosphatidylinositol), which may be anchored in the lipid bilayer.
Polypeptide toxins
Polypeptide toxins, such as
colicinA 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...
s or
hemolysinHemolysins are exotoxins produced by bacteria that cause lysis of red blood cells in vitro. Visualization of hemolysis of red blood cells in agar plates facilitates the categorization of some pathogenic bacteria such as Streptococcus and Staphylococcus...
s, and certain proteins involved in
apoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, are sometimes considered a separate category. These proteins are water-soluble but can aggregate and associate irreversibly with the lipid bilayer and form alpha-helical or beta-barrel transmembrane channels.
Intracellular localization
Proteins are specifically targeted to many different types of biological membranes
Membrane protein complexes
Membrane proteins commonly function as complexes. These complexes are vital to cellular function. Understanding how these complexes are assembled, degraded, and their composition are crucial to understanding their function and regulation. Reoccurring in recent literature are the ideas that: membrane protein complexes assemble in an orderly fashion, chaperones aid assembly by preventing unfavorable interactions, and membrane proteins can be interchanged in existing complexes.
Membrane protein complexes assemble through the orderly assembly of intermediates. For example, the simple membrane-embedded four subunit complex, cytochrome bo3 of Escherichia coli, is assembled via two intermediate complexes. This suggests a linearly organized assembly pathway. Although interactions between other subunits could lead to the formation of many intermediates, they do not occur. Ordered assembly could be the cell's protection against harmful intermediates.
Chaperones interact with membrane proteins guiding their assembly. They aid in preventing the assembly of dead-end and toxic intermediates, as well as unwanted aggregations. Via chaperones assembly can occur through inactive intermediates potentially preventing damaging interactions they could cause.
Membrane protein complexes are not fixed entities. Though a process called dynamic exchange, membrane proteins are exchanged in and out of exsitisting protein complexes. This has its implications as a repair mechanism and in regulation.
Assembly of membrane protein
There are two different ways a membrane protein could undergoes during construction are Constitutive membrane protein and non-constitutive membrane protein.
Constitutive membrane protein
The messengerRNA attaches to the translocon which is located to the cell membrane. The mRNA is translated into the translocon transmembrane tunnel. After the synthesis of protein the mRNA is released which closes the translocon and the protein is released in the bilayer membrane. When the protein is left in the membrane bilayer more protein folding occurs creating its final 3D structure (White).
Non-constitutive membrane protein
Examples of non-constitutive membrane proteins are toxins and antimicrobialpeptides. These membrane proteins inserts into specific target membranes by physicochemical processes. It inserts usually before, during, or after oligomerization into the target membrane (White).
Membrane protein structures
In membrane proteins the two known structural classes of membrane proteins are alpha-helical bundle and beta-barrel porin. The portion of the membrane proteins that are attached to the lipid bilayer are consisting of hydophobic amino acids only. This is done so that the peptide bonds' carbonyl and amine will react with each other instead of the hydrophobic surrounding. The portion of the protein that is not touching the lipid bilayer and is protruding out of the cell membrane are usually hydrophilic amino acids.
The structures of membrane proteins are stabilized by weak interactions and influenced by additional interactions with the solubilizing environment. The influence of the environment on membrane protein structures is especially significant. Despite the significant functional importance of membrane proteins, the structural biology has been particularly challenging as shown by the low number of membrane protein structures determined. Integral membrane proteins are present in a heterogeneous environment that poses major obstacles for existing structural methodologies.
Many of the successful membrane protein structures are characterized by X-ray crystallography and are very large structures in which the interactions with the membrane mimetic environments can be anticipated to be small in comparison to those within the protein structures. The small domains are particularly sensitive to the influence of membrane mimetic environments, potentially leading to non-native structures. Fortunately, there are many sample preparation conditions that can be chosen for crystallization and for solution NMR. All membrane protein structural biology should be subjected to careful scrutiny; through a combination of structural methodologies it should be possible to achieve an understanding of the native functional state for membrane protein structures.
See also
- Integral membrane protein
An integral membrane protein is a protein molecule 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...
s
- 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
- Peripheral membrane protein
Peripheral 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
- Ion pump (biology)
In biology, an ion transporter, also called an ion pump, is a transmembrane protein that moves ions across a plasma membrane against their concentration gradient, in contrast to ion channels, where ions go through passive transport...
- Carrier protein
Carrier proteins are proteins involved in the movement of ions, small molecules, or macromolecules, such as another protein, across a biological membrane. Carrier proteins are integral membrane proteins; that is they exist within and span the membrane across which they transport substances. The...
- Ion 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...
- 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...
(including G protein-coupled receptorG protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
)
- List of MeSH codes (D12.776)
External links