title: A structural model of the active ribosome-bound membrane protein insertase YidC.
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 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.
authors.affiliation: Gene Center Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany Center for Integrated Protein Science Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Wickles
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, United States.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Singharoy
authors.affiliation: Gene Center Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany Center for Integrated Protein Science Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Andreani
authors.affiliation: Gene Center Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany Center for Integrated Protein Science Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Seemayer
authors.affiliation: Gene Center Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany Center for Integrated Protein Science Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Bischoff
authors.affiliation: Gene Center Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany Center for Integrated Protein Science Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Otto
authors.initials: O
authors.lastname: Berninghausen
authors.affiliation: Gene Center Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany Center for Integrated Protein Science Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Soeding
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, United States.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulten
authors.affiliation: Gene Center Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany Center for Integrated Protein Science Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany vandersluis@lmb.uni-muenchen.de.
authors.forename: Eli O
authors.initials: EO
authors.lastname: van der Sluis
authors.affiliation: Gene Center Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany Center for Integrated Protein Science Munich, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany beckmann@lmb.uni-muenchen.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Beckmann
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006860:Hydrogen Bonding; D007700:Kinetics; D008055:Lipids / Q000737:chemistry; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism; D000069816:SEC Translocation Channels; D016415:Sequence Alignment; D013816:Thermodynamics
chemical_list: D029968:Escherichia coli Proteins; D008055:Lipids; D026901:Membrane Transport Proteins; D000069816:SEC Translocation Channels; C057841:SecY protein, E coli; C412443:YIDC protein, E coli
keywords: YidC; bioinformatics; cryo-EM; molecular dynamics; ribosome