PXD039954

PXD039954 is an original dataset announced via ProteomeXchange.

Title	Structural basis for SMAC-mediated antagonism of caspase inhibition by the giant ubiquitin ligase BIRC6
Description	Certain Inhibitors of apoptosis (IAP) family members are sentinel proteins preventing untimely cell death by inhibiting caspases. Antagonists including second mitochondria-derived activator of caspase (SMAC) regulate IAPs, driving cell death. Baculoviral IAP repeat-containing protein 6 (BIRC6), a giant IAP with dual E2/E3 ubiquitin ligase activity, regulates programmed cell death through unknown mechanisms. We show BIRC6 directly restricts executioner caspases-3 and -7, and ubiquitinates caspases-3, -7 and -9 working exclusively with non canonical E1, UBA6. Importantly, we show SMAC supresses both mechanisms. Cryo-electron microscopy structures of BIRC6 alone and in complex with SMAC reveals BIRC6 is an anti parallel dimer juxtaposing the substrate-binding module against the catalytic domain. Furthermore, we discover SMAC multi-site binding to BIRC6 results in a sub-nanomolar affinity interaction, enabling SMAC to competitively displace caspases thus antagonising BIRC6 anti-caspase function.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:00:37.807.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Adan Pinto-Fernandez
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-08 06:28:39	ID requested
1	2023-03-08 08:32:26	announced
⏵ 2	2023-11-14 08:00:39	announced	2023-11-14: Updated project metadata.

Dietz L, Ellison CJ, Riechmann C, Cassidy CK, Felfoldi FD, Pinto-Fern, á, ndez A, Kessler BM, Elliott PR, Structural basis for SMAC-mediated antagonism of caspase inhibition by the giant ubiquitin ligase BIRC6. Science, 379(6637):1112-1117(2023) [pubmed]

submitter keyword: AP-MS, BIRC6, Structural Biology,Cell death, Ubiquitomics, Biochemistry

Adan Pinto-Fernandez
contact affiliation	Chinese Academy of Medical Sciences Oxford Institute (CAMS) - Nuffield Department of Medicine. University of Oxford
contact email	adan.pintofernandez@ndm.ox.ac.uk
lab head
Adan Pinto-Fernandez
contact affiliation	University of Oxford
contact email	adan.pintofernandez@ndm.ox.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/03/PXD039954

PRIDE project URI

• PRIDE
  1. PXD039954
     1. Label: PRIDE project
     2. Name: Structural basis for SMAC-mediated antagonism of caspase inhibition by the giant ubiquitin ligase BIRC6