Biological membranes are barriers to cells or organelles. The basic unit of most biological membranes is phospholipids, but they also contain a large number of proteins. These proteins, which are interspersed among or loosely attached to phospholipids, are membrane proteins. In eukaryotes and prokaryotes, membrane proteins represent about 20 to 30% of the proteome. Membrane proteins are not only an important component of biological membranes, but also the main undertaker of biological membranes function. Membrane proteins have various functions, including nutrient uptake, energy generation, cellular signaling, ion transport, drug resistance, and maintenance of the cellular structure. Furthermore, mutations or improper folding of membrane proteins is associated with many known diseases. Therefore, they are a very important drug target.

Classification of Membrane Proteins

Membrane proteins can be classified as either peripheral (extrinsic) or integral (intrinsic) ^[1].

• Peripheral proteins are held to the membrane surface primarily through electrostatic or hydrogen bonds, which are essentially water-soluble globular proteins. Therefore, the peripheral membrane proteins can be readily removed from biological membranes without disrupting membrane by simply changing the ionic strength of the medium or adjusting the pH value. The removed protein is freely soluble in water. Peripheral proteins can also be divided into two basic types: those that are attached on the surface of integral proteins and those that are attached on the phospholipid anionic head group ^[2].

• Integral membrane proteins are embedded in the membrane hydrophobic interior to varying extents. They interact extensively with membrane lipids, so they can only be removed from the membrane by more stringent measures. Integral membrane proteins are usually extracted using detergent or mechanical rupture of membrane. The extracted protein is water-insoluble aggregates. Integral membrane proteins are the target of most studies, which accounts for 70 ~ 80% of membrane protein species.

Structure of Membrane Proteins

At present, most studies on the structure of membrane proteins have focused on integral membrane proteins. Integral membrane proteins are classified by their overall structure into two dominant classes: α-helical bundles and β-barrels ^[1].

• α-Helical bundles: α-helix is an important secondary structural unit, which is one of the bases of protein tertiary structure and plays an important role in protein structure and function. In the majority of integral membrane proteins each transmembrane segment (TMS) is an α-helix of twenty or more predominantly nonpolar residues and the presence of one or two polar residues is tolerated. α-helical membrane proteins often appear in plasma membrane, endoplasmic reticulum and mitochondrial intima. The first membrane protein observed by electron microscopy to consist of an α-helical core was bacteriorhodopsin (as shown in Fig. 4) ^[3].
• β-barrels: β-barrels typically consist of an even number (8 to 26) of amphiphilic β-strands crossing the bilayer at a tilt of ∼45°, each containing 9 to 11 residues hydrogen-bonded to the adjacent strands. Membrane-spanning β-barrels are found in the outer membranes of Gram negative bacteria as well as mitochondria and chloroplasts, where they function in transport, phage binding, catalysis, and adhesion.
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