The mechanisms of integral membrane protein biogenesis

• Published in: Nature reviews. Molecular cell biology Vol. 23; no. 2; pp. 107 - 124
• Main Authors: Hegde, Ramanujan S., Keenan, Robert J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-02-2022; Nature Publishing Group
• Subjects: 631/45/470/1463; 631/45/470/1981; 631/80/2023/2022; Animals; Assembly; Biochemistry; Biomedical and Life Sciences; Biosynthesis; Cancer Research; Cell Biology; Developmental Biology; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Eukaryotes; Folding; Humans; Insertion; Integral membrane proteins; Life Sciences; Lipid bilayers; Lipids; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Membranes; Models, Molecular; Prokaryotes; Protein Biosynthesis; Proteins; Proteomes; Review Article; Signal Recognition Particle - metabolism; Stem Cells; Structure-function relationships; Substrate Specificity; Topology
• ISSN: 1471-0072; 1471-0080
• DOI: 10.1038/s41580-021-00413-2

Roughly one quarter of all genes code for integral membrane proteins that are inserted into the plasma membrane of prokaryotes or the endoplasmic reticulum membrane of eukaryotes. Multiple pathways are used for the targeting and insertion of membrane proteins on the basis of their topological and biophysical characteristics. Multipass membrane proteins span the membrane multiple times and face the additional challenges of intramembrane folding. In many cases, integral membrane proteins require assembly with other proteins to form multi-subunit membrane protein complexes. Recent biochemical and structural analyses have provided considerable clarity regarding the molecular basis of membrane protein targeting and insertion, with tantalizing new insights into the poorly understood processes of multipass membrane protein biogenesis and multi-subunit protein complex assembly.
Integral membrane proteins make up around one quarter of the human proteome and are highly diverse in topology, biophysical features, structure and function. Their biogenesis involves multiple pathways for membrane targeting, insertion into the lipid bilayer, folding and assembly with other subunits. Recent biochemical and structural analyses have provided new insights into these mechanisms.