PXD064067

PXD064067 is an original dataset announced via ProteomeXchange.

Title	A heterotrimeric protein complex assembles the metazoan V-ATPase upon dissipation of proton gradients
Description	Organelles like lysosomes and synaptic vesicles are acidified by V-ATPases, which consist of a cytosolically-oriented V1 complex that hydrolyzes ATP and a membrane-embedded VO complex that pumps protons. In yeast, V1-VO association is facilitated by the RAVE complex, but how higher eukaryotes assemble V-ATPases remains unclear. Here, we identify a metazoan RAVE complex (mRAVE) whose structure and composition are notably divergent from the ancestral counterpart. mRAVE consists of DMXL1 or DMXL2, WDR7, and the central linker ROGDI. DMXL1/2 interacts with subunits A and D of the inactive, isolated V1. Upon dissipation of proton gradients, mRAVE binds to V1 and VO, forming a supercomplex on the membrane. mRAVE then catalyzes V1-VO assembly, enabling lysosomal acidification, neurotransmitter loading into vesicles, and ATG16L1 recruitment for LC3/ATG8 conjugation onto single-membranes (CASM). Our findings provide a molecular basis for neurological disorders caused by mRAVE mutations.
HostingRepository	PRIDE
AnnounceDate	2025-05-20
AnnouncementXML	Submission_2025-05-20_13:19:14.273.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christopher Nardone
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carbamoylated residue; monohydroxylated residue
Instrument	Q Exactive HF; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-19 12:11:58	ID requested
⏵ 1	2025-05-20 13:19:14	announced

Dataset with its publication pending

submitter keyword: CX-MS, Affinity Purification

Tom Rapoport
contact affiliation	Harvard Medical School, Department of Cell Biology Howard Hughes Medical Institute
contact email	tom_rapoport@hms.harvard.edu
lab head
Christopher Nardone
contact affiliation	Harvard Medical School
contact email	christopher_nardone@hms.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064067
     1. Label: PRIDE project
     2. Name: A heterotrimeric protein complex assembles the metazoan V-ATPase upon dissipation of proton gradients