PXD033639

PXD033639 is an original dataset announced via ProteomeXchange.

Title	Structure and mechanism of a novel cytomegaloviral DCAF mediating interferon antagonism
Description	Human cytomegalovirus (CMV) is a highly relevant pathogen, and its rodent counterparts serve as common infection models. Global proteome profiling of rat CMV-infected cells uncovered a pronounced loss of the transcription factor STAT2, which is crucial for interferon signalling. Deletion mutagenesis documented that STAT2 is targeted by the viral protein E27. Cellular and in vitro analyses showed that E27 exploits host-derived Cullin4-RING ubiquitin ligases (CRL4) to induce poly-ubiquitylation and proteasomal degradation of STAT2. Cryo-electron microscopic structure determination revealed how E27 mimics molecular surface properties of cellular CRL4 substrate receptors to displace them from DDB1. Moreover, structural analyses elucidated the mechanism of STAT2 recruitment and indicate that E27-binding additionally disturbs STAT2 activation by occupying the IRF9 binding interface. For the first time, these data provide structural insights into cytomegalovirus-encoded interferon antagonism and establish an atomic model for STAT2 counteraction by CRL4 misappropriation with important implications for viral immune evasion.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:56:05.904.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thilo Bracht
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116; scientific name: Rat cytomegalovirus ALL-03; NCBI TaxID: 1640278; scientific name: Cytomegalovirus; NCBI TaxID: NCBITaxon:10358;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-04 14:38:55	ID requested
1	2022-12-09 01:09:03	announced
⏵ 2	2023-11-14 08:56:06	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Interferon

ubiquitin-proteasome system

Cullin-RING ubiquitin ligases (CRL)

DDB1

DCAFs

viral DCAF (vDCAF)

antiviral

cytomegalovirus (CMV)

STAT2

IRF9

Thilo Bracht
contact affiliation	Clinical Proteomics Medizinisches Proteom-Center Ruhr-University Bochum
contact email	thilo.bracht@rub.de
lab head
Thilo Bracht
contact affiliation	Clinical Proteomics
contact email	thilo.bracht@rub.de
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/2022/12/PXD033639

PRIDE project URI

• PRIDE
  1. PXD033639
     1. Label: PRIDE project
     2. Name: Structure and mechanism of a novel cytomegaloviral DCAF mediating interferon antagonism