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

The integration of most membrane proteins into the cytoplasmic membrane of bacteria occurs co-translationally. The universally conserved YidC protein mediates this process either individually as a membrane protein insertase, or in concert with the SecY complex. Here, we present a structural model of YidC based on evolutionary co-variation analysis, lipid-versus-protein-exposure 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 membrane surface. The model was used for docking into a cryo-electron microscopy reconstruction of a translating YidC-ribosome complex carrying the YidC substrate F(O)c. This structure reveals how a single copy of YidC interacts with the ribosome at the ribosomal tunnel exit and identifies a site for membrane protein insertion at the YidC protein-lipid interface. Together, these data suggest a mechanism for the co-translational mode of YidC-mediated membrane protein insertion.