PXD055759-1

PXD055759 is an original dataset announced via ProteomeXchange.

Title	The molecular basis of integrated stress response silencing
Description	Chronic stress response activation impairs cell survival and causes devastating degenerative di-seases. To counteract this, cells deploy dedicated silencing factors, such as the E3 ligase SIFI that terminates the mitochondrial stress response. How a single enzyme can sense stress across cellular scales and elicit timely stress response inactivation is poorly understood. Here, we report the structure of human SIFI, which revealed how this 1.3MDa complex can target hundreds of proteins for accurate stress response silencing. SIFI attaches the first ubiquitin to substrates using flexible domains within an easily accessible scaffold, yet builds linkage-specific ubiquitin chains at distinct, sterically restricted elongation modules in its periphery. Ubiquitin handover via a ubiquitin-like domain couples versatile substrate modification to precise chain elongation. Stress res-ponse silencing therefore exploits a catalytic mechanism that is geared to process many diverse proteins and hence allows a single enzyme to monitor and, if appropriate, modulate a complex cellular state.
HostingRepository	PRIDE
AnnounceDate	2025-04-16
AnnouncementXML	Submission_2025-04-16_12:51:21.544.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex Zelter
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-09 18:28:30	ID requested
⏵ 1	2025-04-16 12:51:21	announced

Dataset with its publication pending

submitter keyword: SIFI,XL-MS, mass spectrometry, ubiquitin, E3 ligase, BS3

Michael J MacCoss
contact affiliation	Department of Genome Sciences, University of Washington
contact email	maccoss@uw.edu
lab head
Alex Zelter
contact affiliation	Department of Biochemistry, University of Washington, Seattle
contact email	azelter@uw.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055759
     1. Label: PRIDE project
     2. Name: The molecular basis of integrated stress response silencing