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TitleStructural Snapshots of 26S Proteasome Reveal Tetraubiquitin-Induced Conformations.
Journal, issue, pagesMol Cell, Vol. 73, Issue 6, Page 1150-11161.e6, Year 2019
Publish dateMar 21, 2019
AuthorsZhanyu Ding / Cong Xu / Indrajit Sahu / Yifan Wang / Zhenglin Fu / Min Huang / Catherine C L Wong / Michael H Glickman / Yao Cong /
PubMed AbstractThe 26S proteasome is the ATP-dependent protease responsible for regulating the proteome of eukaryotic cells through degradation of mainly ubiquitin-tagged substrates. In order to understand how ...The 26S proteasome is the ATP-dependent protease responsible for regulating the proteome of eukaryotic cells through degradation of mainly ubiquitin-tagged substrates. In order to understand how proteasome responds to ubiquitin signal, we resolved an ensemble of cryo-EM structures of proteasome in the presence of K48-Ub, with three of them resolved at near-atomic resolution. We identified a conformation with stabilized ubiquitin receptors and a previously unreported orientation of the lid, assigned as a Ub-accepted state C1-b. We determined another structure C3-b with localized K48-Ub to the toroid region of Rpn1, assigned as a substrate-processing state. Our structures indicate that tetraUb induced conformational changes in proteasome could initiate substrate degradation. We also propose a CP gate-opening mechanism involving the propagation of the motion of the lid to the gate through the Rpn6-α2 interaction. Our results enabled us to put forward a model of a functional cycle for proteasomes induced by tetraUb and nucleotide.
External linksMol Cell / PubMed:30792173
MethodsEM (single particle)
Resolution3.8 - 7.5 Å
Structure data

EMDB-9769, PDB-6j2c:
Yeast proteasome in translocation competent state (C3-a)
Method: EM (single particle) / Resolution: 7 Å

EMDB-9770, PDB-6j2n:
yeast proteasome in substrate-processing state (C3-b)
Method: EM (single particle) / Resolution: 7.5 Å

EMDB-9771, PDB-6j2q:
Yeast proteasome in Ub-accepted state (C1-b)
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-9772, PDB-6j2x:
Yeast proteasome in resting state (C1-a)
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-9773, PDB-6j30:
yeast proteasome in Ub-engaged state (C2)
Method: EM (single particle) / Resolution: 4.5 Å

Source
  • saccharomyces cerevisiae s288c (yeast)
  • Baker's yeast (baker's yeast)
KeywordsHYDROLASE / Proteasome / K48-Ub4 / Ub-bound / cryo-EM

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