Substrate-engaged 26 S proteasome structures reveal mechanisms for ATP-hydrolysis-driven translocation.

Autor: de la Peña AH; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA., Goodall EA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.; California Institute for Quantitative Biosciences, University of California at Berkeley, Berkeley, CA 94720, USA., Gates SN; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.; California Institute for Quantitative Biosciences, University of California at Berkeley, Berkeley, CA 94720, USA.; Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, CA 94720, USA., Lander GC; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA. glander@scripps.edu a.martin@berkeley.edu., Martin A; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. glander@scripps.edu a.martin@berkeley.edu.; California Institute for Quantitative Biosciences, University of California at Berkeley, Berkeley, CA 94720, USA.; Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, CA 94720, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2018 Nov 30; Vol. 362 (6418). Date of Electronic Publication: 2018 Oct 11.
DOI: 10.1126/science.aav0725
Abstrakt: The 26 S proteasome is the primary eukaryotic degradation machine and thus is critically involved in numerous cellular processes. The heterohexameric adenosine triphosphatase (ATPase) motor of the proteasome unfolds and translocates targeted protein substrates into the open gate of a proteolytic core while a proteasomal deubiquitinase concomitantly removes substrate-attached ubiquitin chains. However, the mechanisms by which ATP hydrolysis drives the conformational changes responsible for these processes have remained elusive. Here we present the cryo-electron microscopy structures of four distinct conformational states of the actively ATP-hydrolyzing, substrate-engaged 26 S proteasome. These structures reveal how mechanical substrate translocation accelerates deubiquitination and how ATP-binding, -hydrolysis, and phosphate-release events are coordinated within the AAA+ (ATPases associated with diverse cellular activities) motor to induce conformational changes and propel the substrate through the central pore.
(Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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