Membrane protein



A 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
Biological membranes consist of a phospholipid bilayer and a variety of proteins that accomplish vital biological functions.
 * Structural proteins are attached to microfilaments in the cytoskeleton which ensures stability of the cell.
 * Cell adhesion molecules 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 proteins serve as connection between the cell's internal and external environments.
 * Transport proteins play an important role in the maintenance of concentrations of ions. These transport proteins come in two forms: carrier proteins and channel proteins.

Main categories
Membrane proteins can be divided into several categories:


 * Integral membrane proteins which are permanently bound to the lipid bilayer
 * 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 proteins are permanently attached to the membrane. They can be defined as those proteins which require a detergent (such as SDS 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. The alpha-helical domains are present in all types of biological membranes including outer membranes. 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 proteins 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 temporarily attached either to the lipid bilayer 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 pH or high salt concentrations.

Integral and peripheral proteins may be post-translationally modified, with added fatty acid or prenyl chains, or GPI (glycosylphosphatidylinositol), which may be anchored in the lipid bilayer.

Polypeptide toxins
Polypeptide toxins, such as colicins or hemolysins, and certain proteins involved in apoptosis, 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.

Membrane Protein Structures
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.