A structural model of the active ribosome-bound membrane protein insertase YidC

By Stephan Wickles, A. Singharoy, Jessica Andreani, Stefan Seemayer, L. Bischoff, O. Berninghausen, J. Soeding, Klaus Schulten, E. O. van der Sluis, Roland Beckmann. 2014

87 citations recorded by the source corpus.

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 FOc. 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. DOI: http://dx.doi.org/10.7554/eLife.03035.001

Subfields: Genetics, Molecular Biology

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Citations in the corpus

Large-scale determination of previously unsolved protein structures using evolutionary information (2015, methodology): “Distance restraints derived from such predictions have been used to model a wide range of unknown protein structures ( Hayat et al., 2014 ; Wickles et al., 2014 ; Abriata, 2015 ; Antala et al., 2015 ; Hopf et al., 2015 ; Tian et al., 2015 ) and protein–protein complexes ( Ovchinnikov et al., 2014 ;…”
Scalable molecular dynamics on CPU and GPU architectures with NAMD. (2020, methodology): “It has proven to be an extremely successful refinement method as evidenced by its numerous applications 215,225 ranging from the intricate ribosomal machinery 216,226–228 to a host of non-enveloped viruses.”
Structural Dynamics of the YidC:Ribosome Complex during Membrane Protein Biogenesis (2016, background): “Structure of the YidC-ND:RNC Complex Current knowledge of the YidC:ribosome complex architecture is largely based on cryo-EM structures observed in the detergent environment (Seitl et al., 2014; Wickles et al., 2014).”