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PXD081081

PXD081081 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe ER membrane protein complex acts as a chaperone to promote the biogenesis of multi-bundle membrane proteins
DescriptionNearly half of the ~5,000 human membrane proteins need to assemble into stoichiometric complexes as part of their biogenesis at the endoplasmic reticulum (ER) membrane. How ER resident biogenesis factors coordinate membrane insertion, folding and assembly is not well understood. Here, we demonstrate that the ER membrane protein complex (EMC) insertase additionally acts as a chaperone to facilitate the assembly of heterotrimeric voltage-gated calcium channels (Cav). Using function-separating mutations and inhibitory nanobodies we show that nascent Cav channels are degraded prematurely when EMC's chaperone function is selectively perturbed. Blocking EMC's chaperone function strongly impaired Cav-dependent cardiomyocyte contraction. EMC engagement of the pore-forming Cav alpha-subunit occurred co-translationally and required Cav alpha's first transmembrane domain bundle to protrude from the nascent ribosome Sec61 multipass translocon complex. Our findings establish a chaperone function for the EMC and reveal that biogenesis of multi-bundle membrane proteins requires a highly orchestrated, co-translational interplay between ER biogenesis factors.
HostingRepositoryMassIVE
AnnounceDate2026-08-28
AnnouncementXMLSubmission_2026-08-28_13:56:41.644.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDain Brademan
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListCarbamidomethyl; Oxidation
InstrumenttimsTOF HT
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-07-14 15:43:08ID requested
12026-08-28 13:56:42announced
Publication List
no publication
Keyword List
submitter keyword: timsTOF, dia-PASEF, bottom-up proteomics, DatasetType:Proteomics
Contact List
Ruth Huttenhain
contact affiliationDepartment of Molecular and Cellular Pharmacology, UCSF
contact emailRuth.huttenhain@ucsf.edu
lab head
Dain Brademan
contact affiliationStanford School of Medicine
contact emailbrademan@stanford.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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