Dynamics of SecY translocons with translocation-defective mutations.

Structure
Ana-Nicoleta BondarStephen H White

Abstract

The SecY/Sec61 translocon complex, located in the endoplasmic reticulum membrane of eukaryotes (Sec61) or the plasma membrane of prokaryotes (SecY), mediates the transmembrane secretion or insertion of nascent proteins. Mutations that permit the secretion of nascent proteins with defective signal sequences (Prl-phenotype), or interfere with the transmembrane orientation of newly synthesized protein segments, can affect protein topogenesis. The crystallographic structure of SecYEbeta from Methanococcus jannaschii revealed widespread distribution of mutations causing topogenesis defects, but not their molecular mechanisms. Based upon prolonged molecular dynamics simulations of wild-type M. jannaschii SecYEbeta and an extensive sequence-conservation analysis, we show that the closed state of the translocon is stabilized by hydrogen-bonding interactions of numerous highly conserved amino acids. Perturbations induced by mutation at various locations are rapidly relayed to the plug segment that seals the wild-type closed-state translocon, leading to displacement and increased hydration of the plug.

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Citations

Oct 23, 2012·Cell Reports·Bin Zhang, Thomas F Miller
Jul 28, 2012·The Journal of Membrane Biology·Coral Del ValAna-Nicoleta Bondar
Sep 22, 2010·Proceedings of the National Academy of Sciences of the United States of America·Pascal F Egea, Robert M Stroud
Oct 29, 2011·The Journal of Biological Chemistry·Jelger A Lycklama A NijeholtArnold J M Driessen
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Dec 12, 2012·The Journal of Cell Biology·Steven F TruemanReid Gilmore
Jul 4, 2015·Proceedings of the National Academy of Sciences of the United States of America·Sara CapponiStephen H White
Jun 3, 2011·Trends in Cell Biology·Kush Dalal, Franck Duong
Nov 27, 2015·Biochimica Et Biophysica Acta·Stefan Milenkovic, Ana-Nicoleta Bondar
Dec 20, 2011·Biochimica Et Biophysica Acta·Ana-Nicoleta Bondar, Stephen H White
Jun 13, 2015·The Journal of Membrane Biology·Zoe CourniaAna-Nicoleta Bondar
Sep 16, 2015·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Ian CollinsonWilliam J Allen
Apr 17, 2012·Biochimica Et Biophysica Acta·Ana-Nicoleta Bondar, Holger Dau
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Jun 16, 2018·FEMS Microbiology Letters·Konstantina Karathanou, Ana-Nicoleta Bondar
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Mar 29, 2018·The Journal of Physical Chemistry. B·Federico GuerraAna-Nicoleta Bondar
Apr 26, 2019·Chemical Reviews·Ana-Nicoleta Bondar, M Joanne Lemieux

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