PXD010023

PXD010023 is an original dataset announced via ProteomeXchange.

Title	Transportin-1 (TRN-1) orchestrates HIV-1 uncoating and nuclear import
Description	Timely uncoating and nuclear import are key to efficient HIV infection, however the triggers and mechanisms that orchestrate these steps are unknown. Here we show that HIV-1 exploits Transportin-1/TRN-1 for both uncoating and nuclear import. Depletion of TRN-1, which we characterised by mass spectrometry, significantly reduced the early steps of HIV-1 infection in cell lines and primary CD4+ T cells. We showed that TRN-1 binds to incoming HIV-1 capsid (CA) cores, but not monomeric CA or integrase, via a NLS present on the cyclophilin A (CypA) binding loop. The G89V mutant, but not P90A, relieved dependency on TRN-1, and TRN-1 binding to CA at position G89 displaced CypA, which likely contributes to weakening the CA assembly. Recombinant TRN-1 could induce CA uncoating in vitro indicating that disruption is entirely mechanical, and activity mapped to residue W730 that plays a pivotal role in binding to substrate NLS. HIV-1 intercepts TRN-1 near the nuclear envelope and complexes that fail to do so scatter back into the cytoplasm without uncoating. For complexes that uncoat, TRN-1 mediates the concomitant nuclear import of CA and viral DNA. Our study reveals how HIV-1 uses a single cellular protein to orchestrate the key steps that allow it to reach its replication compartment efficiently.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:45:42.093.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thibaut LEGER
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-04 05:39:36	ID requested
1	2019-09-25 07:12:42	announced
2	2019-11-06 00:29:51	announced	2019-11-06: Updated publication reference for PubMed record(s): 31611641.
⏵ 3	2024-10-22 04:45:50	announced	2024-10-22: Updated project metadata.

Fernandez J, Machado AK, Lyonnais S, Chamontin C, G, ä, rtner K, L, é, ger T, Henriquet C, Garcia C, Portilho DM, Pugni, è, re M, Chaloin L, Muriaux D, Yamauchi Y, Blaise M, Nisole S, Arhel NJ, Transportin-1 binds to the HIV-1 capsid via a nuclear localization signal and triggers uncoating. Nat Microbiol, 4(11):1840-1850(2019) [pubmed]

10.1038/s41564-019-0575-6;

curator keyword: Biological

submitter keyword: TRN-1, co-immunoprecipitation, human, transportin-1, HIV, nuclear import, Orbitrap Fusion

Nathalie Arhel
contact affiliation	Nathalie Arhel Team leader "Viral Trafficking, Restriction & Innate Signaling (VTRIS) Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) CNRS FRE3689 - Montpellier University 1919 route de Mende, 34293 Montpellier cedex 5, France Room 173 / Phone: +33 (0)4 34 35 94 53 / Fax: +33 (0)4 34 35 94 11 Lab web page: http://www.cpbs.cnrs.fr/ Laboratory of Excellence EpigenMed: http://www.epigenmed.fr/
contact email	nathalie.arhel@irim.cnrs.fr
lab head
Thibaut LEGER
contact affiliation	EHESP/LERES
contact email	thibaut.leger@ehesp.fr
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/2019/09/PXD010023

PRIDE project URI

• PRIDE
  1. PXD010023
     1. Label: PRIDE project
     2. Name: Transportin-1 (TRN-1) orchestrates HIV-1 uncoating and nuclear import