TCB Publications - Abstract

Stephan Wickles, Abhishek Singharoy, Jessica Andreani, Stefan Seemayer, Lukas Bischoff, Otto Berninghausen, Johannes Soeding, Klaus Schulten, Eli van der Sluis, and Roland Beckmann. A structural model of the active ribosome-bound membrane protein insertase YidC. eLife, 3:e03035, 2014. (PMC: PMC4124156)

WICK2014 The integration of most membrane proteins into the cytoplasmic membrane of bacteria occurs co-translationally. The universally conserved YidC protein can mediate this process either individually as a membrane protein insertase, or as a membrane protein chaperone in concert with the canonical protein-conducting channel, the SecY complex (Kol, Nouwen et al. 2008; Dalbey, Wang et al. 2011). However, little is known about the structural basis of YidC's ribosome interaction and co-translational insertion activity. Here, we present a structural model of YidC based on evolutionary co-variation analysis (Hopf, Colwell et al. 2012), lipid versus protein exposure (Lai, Cheng et al. 2013) and molecular dynamics simulations. The model suggests a distinctive arrangement of the conserved five transmembrane domains and a helical hairpin between transmembrane segment 2 (TM2) and TM3 on the cytoplasmic surface of the bilayer. The model was used for docking into a cryo-electron microscopy reconstruction of a translating YidC-ribosome complex carrying the YidC substrate F$_\textrm{o}$c. This structure reveals how a single copy of YidC interacts with the ribosome at the ribosomal tunnel exit and suggests a site for membrane protein insertion at the YidC protein-lipid interphase. This site was confirmed by chemical crosslinking of F$_\textrm{o}$c to TM3 of YidC. Together, these data suggest a mechanism for the co-translational mode of YidC-mediated membrane protein insertion.

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