12.10:
Single-pass Transmembrane Proteins
Transmembrane proteins are embedded in the lipid bilayer and have domains on either side of the membrane in addition to their transmembrane domains. They constitute about 25% of the proteins coded in the human genome and have various roles, including transporters, enzymes, and receptors.
The transmembrane domain, the membrane-spanning region of the protein, contains non-polar amino acids that form hydrophobic sections. In contrast, the cytosolic and exoplasmic domains are often hydrophilic.
Depending on the number of times the polypeptide chain crosses the membrane, transmembrane proteins can be classified as either single-pass or multi-pass proteins.
A single-pass protein contains approximately 20 to 30 non-polar amino acid residues spanning the membrane. This pass is most often an alpha-helix positioned vertically or slanted in the membrane.
In an alpha helix, the carbonyl and amide groups in the peptide backbone form hydrogen bonds, while the non-polar side groups point outwards into the hydrophobic environment of the membrane.
Single-pass proteins may form homo- or hetero-oligomers through non-covalent interactions.
12.10:
Single-pass Transmembrane Proteins
Integral membrane proteins are tightly associated with the cell membrane and play a crucial role in cell communication, signaling, adhesion, and transport of the molecules. Some integral membrane proteins are present only in the membrane monolayer. For example, the enzyme fatty acid amide hydrolase is present in the cytoplasmic side of the membrane monolayer. In contrast, another type of integral membrane protein, also known as a transmembrane protein, spans across the membrane. Transmembrane proteins contain the cytoplasmic, transmembrane, and exoplasmic domains. Proteins embedded only in the membrane, without having an exoplasmic or cytoplasmic domain, are not yet discovered.
Single-pass membrane proteins, like receptor tyrosine kinase, contain only one transmembrane α-helix domain. In the majority of membrane proteins, the transmembrane domain is α-helix containing around 20-30 non-polar amino acids. This characteristic amino acid sequence in the α-helix of the transmembrane proteins is used to identify the potential transmembrane domains present in a protein using the hydropathy plot. The free energy required to transfer an amino acid from an aqueous to a lipid medium is used to generate the hydropathy plot. The average energy values of the polypeptide segments give information about potential transmembrane domains present in a protein. A hydropathy plot can help identify whether a particular protein is a single-pass or multi-pass membrane protein.
Transmembrane proteins play an essential role in a cell's interaction with the extracellular environment. Therefore, transmembrane proteins are the target for more than 50% of the available drugs and are of great pharmacological importance. A better knowledge of the structure and function of transmembrane proteins can help understand the pathogenesis of several diseases and the relevant drug discovery.