PXD030332

PXD030332 is an original dataset announced via ProteomeXchange.

Title	Mechanistic and structural bases for avid CPSF6 binding to HIV-1 capsid lattices
Description	Cellular proteins CPSF6, NUP153 and SEC24C play crucial roles in HIV-1 infection. While weak interactions of short FG peptides to isolated capsid hexamers have been characterized, how these proteins engage biologically relevant extended HIV-1 capsid lattices is unknown. We have identified that prion-like low complexity regions (LCR) enable avid binding of CPSF6, NUP153 and SEC24C to curved hexameric capsid lattices. Structural studies reveal that LCR-LCR interactions mediate multivalent CPSF6 assembly, which are templated by binding of CPSF6 FG peptides to a subset of hydrophobic capsid pockets positioned along adjoining hexamers. CPSF6 LCR mediated avid binding to HIV-1 cores is essential for functional virus-host interactions in infected cells. Investigational drug lenacapavir can access unoccupied hydrophobic pockets in the CPSF6-HIV-1 complex and potently impair HIV-1 inside the nucleus without displacing the tightly bound cellular cofactor from virus cores. These results elucidate previously undescribed mechanisms of virus-host interactions and potent inhibition of HIV-1.
HostingRepository	PRIDE
AnnounceDate	2022-08-31
AnnouncementXML	Submission_2022-08-31_09:34:02.040.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Valentine Courouble
SpeciesList	scientific name: Human immunodeficiency virus; NCBI TaxID: 12721; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-12 05:29:57	ID requested
⏵ 1	2022-08-31 09:34:02	announced

Dataset with its publication pending

submitter keyword: HDX-MS, CPSF6, HIV-1

Patrick Griffin
contact affiliation	Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA.
contact email	pgriffin@scripps.edu
lab head
Valentine Courouble
contact affiliation	Scripps Research
contact email	vcouroub@scripps.edu
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/2022/08/PXD030332

PRIDE project URI

• PRIDE
  1. PXD030332
     1. Label: PRIDE project
     2. Name: Mechanistic and structural bases for avid CPSF6 binding to HIV-1 capsid lattices