Structural Snapshots of 26S Proteasome Reveal Tetraubiquitin-Induced Conformations.
Mol Cell
; 73(6): 1150-1161.e6, 2019 03 21.
Article
em En
| MEDLINE
| ID: mdl-30792173
ABSTRACT
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-Ub4, 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-Ub4 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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Proteínas de Saccharomyces cerevisiae
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Ubiquitina
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Complexo de Endopeptidases do Proteassoma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article