Although membrane lipids form the basic structure of lipid bilayers, the membrane's active function depends on the protein. Cell adhesion, energy transduction, signaling, cell recognition and transport are just some of the important biological processes that membrane proteins carry out. Proteins can bind to the membrane in one of three ways. Inherent or intact membrane proteins are embedded in the hydrophobic regions of the lipid bilayer. Experimentally, these proteins can only be isolated by physically destroying the membrane with a detergent or other non-polar solvent. The Mono Save theme protein is inserted into a leaflet but does not cross the membrane. Transmembrane proteins are classic examples of intrinsic membrane proteins. They span the membrane, usually in an alpha-helical configuration, and can span the membrane multiple times. Some transmembrane proteins use β-barrels to cross the membrane. These structures are usually large and form water-filled channels. External or peripheral membrane proteins loosely bind to the hydrophilic surface of lipid bilayers or intrinsic membrane proteins. They form weak hydrophobic, electrostatic or non-covalent bonds, but do not embed in the hydrophobic core of the membrane. These proteins can be dissociated from the membrane without damaging the membrane by using polar reagents or high pH solutions. External membrane proteins can interact with internal or external leaflets.
Figure 1. Plasma Membrane Proteins.
Plasma Membrane Proteins
There are three ways proteins can associate with the plasma membrane: intrinsic/integral membrane proteins that are embedded in the hydrophobic region of the lipid bilayer, transmembrane proteins that span across the membrane, which can cross the membrane once (single-pass), or multiple times (multi-pass), and extrinsic or peripheral membrane proteins that associate weakly with the hydrophilic surfaces of the lipid bilayer or intrinsic membrane proteins.
1. Integral membrane protein
Integrated memberane protein: Also known as membrane intrinsic protein, which accounts for 70% to 80% of the total membrane protein. It is mainly characterized by water insolubility, its amino acid composition is highly hydrophobic, and it also has hydrophilic amino acids. The constituents penetrate deep into the hydrophobic region of the lipid bilayer and covalently bind to the fatty acid chain. They can be distributed in the lipid bilayer or across the entire membrane. Some are in the form of multi-enzyme complexes, which are composed of intrinsic and peripheral proteins, while others are asymmetrically embedded in the lipid bilayer. These intrinsic proteins can only dissolve from the membrane when treated with a more powerful detergent.
Figure 2. E=extracellular space; P=plasma membrane; I=intracellular space.
IMPs include transporters, linkers, channels, receptors, enzymes, membrane structure anchoring domains, proteins involved in energy accumulation and conduction, and proteins responsible for cell adhesion. The transporter classification can be found in the transporter classification database. An example of the relationship between IMP (in this case, bacterial light-trapping pigment, bacterial rhodopsin) and a membrane formed by a phospholipid bilayer is shown below. In this case, the intact membrane protein straddles the phospholipid bilayer seven times. The part of the protein embedded in the hydrophobic region of the double layer is an alpha helix, which is mainly composed of hydrophobic amino acids. The C-terminus of the protein is in the cytoplasm, while the N-terminal region is outside the cell. A membrane containing this specific protein can play a role in photosynthesis.
2. Transmembrane protein (TP)
Transmembrane protein (TP) is a transmembrane protein that covers the entire cell membrane. Many transmembrane proteins act as channels to allow specific substances to be transported across the membrane. They often undergo significant conformational changes to pass matter through the membrane. They are usually highly hydrophobic and aggregate and precipitate in water. They require extraction with detergents or non-polar solvents, although some of them (beta buckets) can also be extracted with denaturants. The peptide sequence of the transmembrane or transmembrane segment is highly hydrophobic and can be visualized using a hydrophilic map. Depending on the number of transmembrane fragments, transmembrane proteins can be classified as single-span (or double-site) or multi-span (multi-site). Some other indispensable membrane proteins are called unit membrane proteins, which means they are also permanently attached to the membrane but do not pass through the membrane.
Figure 3. Transmembrane protein (TP).
3. Peripheral membrane proteins
Peripheral membrane proteins refer to membrane proteins that interact weakly with the inner and outer surfaces of the membrane by interacting with the polar head of membrane lipids or the ions of inner membrane proteins and forming hydrogen bonds.
Figure 4. Peripheral membrane proteins.
1. Manor, Joshua.; et al. Environment Polarity in Proteins Mapped Noninvasively by FTIR Spectroscopy. The Journal of Physical Chemistry Letters. 2012, 3 (7): 939–944.
2. Wallin E.; et al. Genome-wide analysis of integral membrane proteins from eubacterial, archaean, and eukaryotic organisms. Protein Science. 1998, 7 (4): 1029–38.