9i78

Publication Abstract from PubMed

During the biogenesis of most eukaryotic integral membrane proteins (IMPs), transmembrane domains are inserted into the endoplasmic reticulum membrane by a dedicated insertase or the SEC61 translocon. The SRP-independent (SND) pathway is the least understood route into the membrane, despite catering for a broad range of IMP types. Here, we show that Chaetomium thermophilum SND3 is a membrane insertase with an atypical fold. We further present a cryo-electron microscopy structure of a ribosome-associated SND3 translocon complex involved in co-translational IMP insertion. The structure reveals that the SND3 translocon additionally comprises the complete SEC61 translocon, CCDC47 and TRAPa. Here, the SEC61beta N-terminus works together with CCDC47 to prevent substrate access to the translocon. Instead, molecular dynamics simulations show that SND3 disrupts the lipid bilayer to promote IMP insertion via its membrane-embedded hydrophilic groove. Structural and sequence comparisons indicate that the SND3 translocon is a distinct multipass translocon in fungi, euglenozoan parasites and other eukaryotic taxa.

SND3 is the membrane insertase within a distinct SEC61 translocon complex.,Yang TJ, Mukherjee S, Langer JD, Hummer G, McDowell MA Nat Commun. 2025 Oct 29;16(1):9566. doi: 10.1038/s41467-025-65357-z. PMID:41162385^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.