Excitingly, we find that the SND3 translocon has an analogous organisation to the metazoan multipass translocon, indicating that fungi and other eukaryotic taxa have evolved a distinct, reduced-complexity machinery for the insertion of multipass membrane proteins.

Indeed, molecular dynamics simulations show that SND3 disrupts the lipid bilayer and promotes lipid scrambling via its membrane-embedded hydrophilic groove, suggesting that SND3 is a membrane insertase with a novel fold.

Within this Snd3 translocon complex, CCDC47 and the SEC61β N-terminus keep the SEC61 translocon ‘out of action’, indicating that substrate insertion proceeds via another route.

Proud to share our first lab pre-print: “SND3 is the membrane insertase within a fungal multipass translocon” where @tzujingyang.bsky.social solved the structure of a ribosome-associated SND3-translocon complex involved in ER membrane protein insertion ➡️ doi.org/10.1101/2025...