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TitleSND3 is the membrane insertase within a distinct SEC61 translocon complex.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 9566, Year 2025
Publish dateOct 29, 2025
AuthorsTzu-Jing Yang / Saumyak Mukherjee / Julian D Langer / Gerhard Hummer / Melanie A McDowell /
PubMed AbstractDuring 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. ...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 TRAPɑ. Here, the SEC61β 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.
External linksNat Commun / PubMed:41162385 / PubMed Central
MethodsEM (single particle)
Resolution2.2 - 2.64 Å
Structure data

52656

9i78

EMDB-52656, PDB-9i78:
Cryo-EM structure of Chaetomium thermophilum ribosome-bound SND3 translocon
Method: EM (single particle) / Resolution: 2.2 Å

EMDB-52829: Cryo-EM structure of Chaetomium thermophilum ribosome-bound SND3 translocon complex with improved density for TRAP alpha luminal domain
Method: EM (single particle) / Resolution: 2.64 Å

Chemicals

ChemComp-MG:
Unknown entry

Source
  • thermochaetoides thermophila dsm 1495 (fungus)
KeywordsRIBOSOME / membrane protein biogenesis / SND3 / co-translation translocation / insertase

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