PXD045186

PXD045186 is an original dataset announced via ProteomeXchange.

Title	Chloride intracellular channel (CLIC) proteins function as fusogens
Description	The Cl- intracellular channel (CLIC) family members uniquely transition between soluble and membrane-associated conformations. Despite decades of extensive functional and structural studies, CLICs’ function as ion channels remains debated, rendering our understanding of their physiological role incomplete. Here, we expose a novel function of CLIC5 as a fusogen. We demonstrate that purified CLIC5 directly interacts with the membrane and induces fusion, as reflected by increased liposomal diameter and lipid and content mixing between liposomes. Moreover, we show that this activity is facilitated by acidic pH, a known trigger for CLICs’ transition to a membrane-associated conformation and that increased exposure of the hydrophobic inter-domain interface is crucial for this process. Finally, mutation of a conserved hydrophobic interfacial residue diminishes the fusogenic activity of CLIC5 in vitro and impairs excretory canal formation in C. elegans in vivo. Together, our results unravel the long-sought physiological role of these enigmatic proteins.
HostingRepository	PRIDE
AnnounceDate	2024-03-10
AnnouncementXML	Submission_2024-03-10_04:00:06.809.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pavla Vankova
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-07 02:44:14	ID requested
⏵ 1	2024-03-10 04:00:07	announced

10.1038/S41467-024-46301-Z;

ProteomeXchange project tag: Hydrogen Deuterium Exchange (HDX-MS)

submitter keyword: CLIC protein family, fusogenic activity, CLIC5, HDX-MS

Dr Petr Man
contact affiliation	Laboratory of Structural Biology and Cell Signaling Institute of Microbiology of the Czech Acad Sci Prumyslova 595 252 50 Vestec Czech Republic
contact email	pman@biomed.cas.cz
lab head
Pavla Vankova
contact affiliation	Institute of Biotechnology of the Czech Academy of Sciences, BioCeV, Prumyslova 595, 252 50 Vestec, Czech Republic
contact email	pavla.vankova@ibt.cas.cz
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/2024/03/PXD045186

PRIDE project URI

• PRIDE
  1. PXD045186
     1. Label: PRIDE project
     2. Name: Chloride intracellular channel (CLIC) proteins function as fusogens