PXD047232-2

PXD047232 is an original dataset announced via ProteomeXchange.

Title	The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L binding
Description	Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1 and FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have slightly attenuated replication in vitro and reduced levels of viral antigen in lungs during early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight to the possible underlying molecular defects in fragile X syndrome.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:18:52.981.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fabian Coscia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF SCP; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-25 03:37:28	ID requested
1	2023-12-28 11:40:16	announced
⏵ 2	2024-10-22 06:18:53	announced	2024-10-22: Updated project metadata.

10.1038/S44319-023-00043-Z;

submitter keyword: SARS-CoV-2, UBAP2L, Fragile X syndrome, Stress granules, NSP3

Prof. Dr. Jakob Nilsson
contact affiliation	NNF Center for Protein Research
contact email	jakob.nilsson@cpr.ku.dk
lab head
Fabian Coscia
contact affiliation	Max Delbrueck Center for Molecular Medicine
contact email	fabian.coscia@cpr.ku.dk
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/2023/12/PXD047232

PRIDE project URI

• PRIDE
  1. PXD047232
     1. Label: PRIDE project
     2. Name: The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L binding