Structural insights into the membrane chaperones for multi-pass membrane protein biogenesis

Certain transmembrane a-helices of multi-pass membrane proteins line substrate transport paths or catalytic pockets and, therefore, are partially hydrophilic. Sec61 alone is insufficient to insert these less hydrophobic segments into the membrane and needs to work with dedicated membrane chaperones. Three such membrane chaperones have been described in the literature-the endoplasmic reticulum membrane protein complex (EMC), the TMCO1 complex, and the PAT complex. Recent structural studies on these membrane chaperones have revealed their overall architecture, multi-subunit assem-bly, putative substrate transmembrane helix-binding pockets, and cooperative mechanisms with the ribosome and Sec61 translocon. These structures are providing initial insights into the poorly understood processes of multi-pass membrane protein biogenesis.

Automated summary

Certain transmembrane α-helices of multi-pass membrane proteins have partially hydrophilic regions that form substrate transport paths or catalytic pockets. Sec61 alone is insufficient for inserting these less hydrophobic segments into the membrane and requires dedicated membrane chaperones. Recent structural studies on these chaperones provide insights into the poorly understood process of multi-pass membrane protein biogenesis, including their architecture, multi-subunit assembly, substrate transmembrane helix-binding pockets, and cooperative mechanisms with ribosomes and Sec61 translocons.