In multi-pass membrane proteins, the interaction between multiple transmembrane domains determines their structure and function.
G protein-coupled receptors are the largest family of membrane proteins. They contain seven transmembrane alpha-helices which act to transmit signals between the cell's extracellular and intracellular environments.
In contrast, many channel-forming membrane proteins, such as porins, contain multiple beta-strands of the protein. These form hydrogen bonds to form a continuous cylindrical beta-sheet, creating a rigid ring-like structure called a beta-barrel.
The amino acids in the strands alternate between polar and non-polar residues. Non-polar groups point towards the outside of the barrel and interact with the hydrophobic membrane.
The polar side chains orient towards the inner hydrophilic opening, which forms a channel from the extracellular to intracellular space allowing the passage of small polar solutes.
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and bacteriorhodopsin contain multiple transmembrane domains. All GPCRs have seven transmembrane α-helices, but each receptor has its specific extracellular domain and G-protein-binding site. GPCRs bind a ligand and activate membrane protein called G-protein. The activated G-protein then interacts with either an ion channel or an enzyme in the membrane.
Bacteriorhodopsin found in certain photosynthetic bacteria has seven transmembrane α-helices. It is a light-driven proton pump that helps in ATP production by generating a proton gradient across the membrane.
Some bacterial membrane proteins contain transmembrane β-strands, which are arranged into a ring-like structure called the β-barrel. A minimum of eight β-strands are required to form the barrel-like structure where the edges of the two closely spaced β-strands form hydrogen bonds together. The porin protein observed in the membrane of some gram-negative bacteria contains a transmembrane β-barrel. Apart from bacteria, porin proteins are also found in mitochondrial and chloroplast membranes, which support the hypothesis that both mitochondria and chloroplast are evolved from prokaryotes.