PXD029402-1

PXD029402 is an original dataset announced via ProteomeXchange.

Title	Allosteric control of Ubp6 and the proteasome via a bidirectional switch
Description	The proteasome recognizes target proteins that have been covalently marked by ubiquitin chains. The ubiquitin signal is subject to rapid editing at the proteasome, allowing it to reject substrates based on topological features of their attached ubiquitin chains. Editing is mediated by a key regulator of the proteasome, deubiquitinating enzyme Ubp6. The proteasome activates Ubp6, whereas Ubp6 inhibits the proteasome–both by deubiquitinating proteasome-bound ubiquitin conjugates, and through a noncatalytic effect that does not involve deubiquitination. We report mutants in both Ubp6 and proteasome subunit Rpt1 that abrogate Ubp6 activation. The Ubp6 mutations fall within its ILR element, defined here, which is conserved from yeast to mammals. The ILR is a component of the BL1 blocking loop, other parts of which obstruct ubiquitin access to the catalytic groove in free Ubp6. Rpt1 docking at the ILR opens the catalytic groove by rearranging not only BL1 but also a novel network of three directly interconnected active-site-blocking loops. Ubp6 activation and noncatalytic proteasome inhibition by Ubp6 are linked in that they were eliminated by the same Ubp6 and Rpt1 mutations. Ubp6 and ubiquitin together drive the proteasome into a unique conformational state associated with proteasome inhibition. Our results identify a multicomponent allosteric switch that exerts simultaneous control over the activity of both Ubp6 and the proteasome, and suggest that their active states are in general mutually exclusive.
HostingRepository	PRIDE
AnnounceDate	2022-02-22
AnnouncementXML	Submission_2022-02-22_05:58:05.617.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	John R. Engen
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-28 06:42:12	ID requested
⏵ 1	2022-02-22 05:58:07	announced

Hung KYS, Klumpe S, Eisele MR, Elsasser S, Tian G, Sun S, Moroco JA, Cheng TC, Joshi T, Seibel T, Van Dalen D, Feng XH, Lu Y, Ovaa H, Engen JR, Lee BH, Rudack T, Sakata E, Finley D, Allosteric control of Ubp6 and the proteasome via a bidirectional switch. Nat Commun, 13(1):838(2022) [pubmed]

submitter keyword: proteasome, ubiquitin, Ubp6, allostery, deubiquitination, HDX-MS, hydrogen exchange mass spectrometry

John R. Engen
contact affiliation	Department of Chemistry & Chemical Biology, Northeastern University
contact email	j.engen@northesterrn.edu
lab head
John R. Engen
contact affiliation	Northeastern University
contact email	j.engen@northeastern.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029402
     1. Label: PRIDE project
     2. Name: Allosteric control of Ubp6 and the proteasome via a bidirectional switch