Substrate specific consequences of central pore mutations in the i-AAA protease Yme1 on substrate engagement

Journal of Structural Biology
Martin Graef, Thomas Langer

Abstract

Two membrane-bound ATP-dependent AAA proteases conduct protein quality surveillance in the inner membrane of mitochondria and control crucial steps during mitochondrial biogenesis. AAA domains of proteolytic subunits are critical for the recognition of non-native membrane proteins which are extracted from the membrane bilayer for proteolysis. Here, we have analysed the role of the conserved loop motif YVG, which has been localized to the central pore in other hexameric AAA(+) ring complexes, for the degradation of membrane proteins by the i-AAA protease Yme1. Proteolytic activity was found to depend on the presence of hydrophobic amino acid residues at position 354 within the pore loop of Yme1. Mutations affected proteolysis in a substrate-specific manner: whereas the degradation of misfolded membrane proteins was impaired at a post-binding step, folded substrate proteins did not interact with mutant Yme1. This reflects most likely deficiencies in the ATP-dependent unfolding of substrate proteins, since we observed similar effects for ATPase-deficient Yme1 mutants. Our findings therefore suggest an essential function of the central pore loop for the ATP-dependent translocation of membrane proteins into a proteolytic cavity form...Continue Reading

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Citations

Oct 22, 2008·Nature Structural & Molecular Biology·Andreas MartinRobert T Sauer
Dec 4, 2009·Proceedings of the National Academy of Sciences of the United States of America·Christoph BieniossekUlrich M Baumann
Oct 21, 2009·Molecular and Cellular Biology·Megan BestwickDennis R Winge
Apr 8, 2011·Annual Review of Biochemistry·Robert T Sauer, Tania A Baker
Sep 29, 2009·Research in Microbiology·Takashi Tatsuta, Thomas Langer
Sep 28, 2007·Traffic·Susan Roehl White, Brett Lauring
Sep 20, 2011·Biochimica Et Biophysica Acta·Sina LangklotzFranz Narberhaus
Oct 18, 2011·Biochimica Et Biophysica Acta·Florian GerdesThomas Langer
Jan 20, 2015·Nature Chemical Biology·Ohad IosefsonRobert T Sauer
Mar 9, 2018·Human Molecular Genetics·Bradley PeterRobert N Lightowlers
Jun 15, 2007·Critical Reviews in Biochemistry and Molecular Biology·Mirko Koppen, Thomas Langer
Oct 11, 2019·Protein Science : a Publication of the Protein Society·Stephanie N Gates, Andreas Martin
May 8, 2007·Annals of the New York Academy of Sciences·Claudia Leidhold, Wolfgang Voos
Jun 8, 2017·Frontiers in Molecular Biosciences·Steven E Glynn
Aug 15, 2017·Biochemistry·Roman M LevytskyyOleh Khalimonchuk

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