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-strandcontaining ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.

α-Helix containing multi-pass transmembrane proteins

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.

β-Strands containing multi-pass transmembrane proteins

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.

Some part of this text is adapted from Openstax, Biology 2e, Section 9.1: Signaling Molecules and Cellular Receptors.