Membrane proteins are proteins associated with or attached to the cellular membrane of cell compartments or organelles of a cell. They represent one of the largest and most important classes of proteins and can be classified as either peripheral or integral. Over the past decades, the number of known human protein-coding
genes has always shifted slightly, but in recent years the absolute number is revolving around 20.000 genes (Piovesan, Antonaros and Vitale et al. 2019; Salzberg, 2018). Around one third of those proteins are secreted or membrane-bound proteins (see Figure 1). Although this being a significant portion of the whole proteome, only a few of them are structurally known. As about half of all approved therapeutics target membrane proteins (see Figure 2),
resolving the structure of these therapeutically relevant membrane proteins is highly favorable for future drug design (Baker, 2010). The membrane proteome and secretome are counted as one of the largest and most important classes of proteins. Membrane proteins are defined as proteins being associated or attached to the membrane of a cell or an organelle inside the cell. They are divided into peripheral and integral proteins. Peripheral membrane proteins are temporally associated with the lipid bilayer but do not fully span the membrane. Attachment to the lipid bilayer is achieved by perforation of peripheral regions or by coupling with integral membrane proteins (see Figure 3, B & C). These integral proteins are permanently embedded, span the entire lipid bilayer, and contain hydrophobic alpha-helical or beta-barrel structures residing inside the membrane. They can be further subdivided into groups such as receptors or channels depending on their cellular function. Together with hydrophilic extra- and intracellular domains, the majority of membrane proteins show an amphipathic character. The amphipathic character additionally produces a signature by which integral membrane proteins can often be identified. This is due to their primary structures containing 19-23 hydrophobic amino acids in their linear sequences, required to span the hydrophobic interior of a membrane. β-barrels with hydrophobic residues pointing to the outside of the barrel can also act as a good indicator of a membrane protein (Yeagle, 2016, The Membranes of Cells).
The critical role of membrane proteinsIn many physiological and pathological processes reagents, transcription factors, proteins or ions need to pass membrane barriers. If successful they trigger signal pathways, send growth and coagulation factors or pass on signals of proteins not able to cross the lipid bilayer, like cytokines. Therefore, membrane proteins are located at a very important intersection of many cellular processes. To do this, membrane proteins take over numerous critical functions like the transport of proteins and ions through special channels or the signal transduction inside many organisms. They are responsible for intercellular junctions or cell-cell recognition as well, enabling swift communication between cells and the effective recognition of foreign cells, being of utmost importance for the immune system. Classification and functions of membrane proteins
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