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PXD031833-2

PXD031833 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTTYH family members form tetrameric complexes at the cell membrane
DescriptionThe conserved Tweety homolog (TTYH) family consists of three paralogs in vertebrates, displaying a ubiquitous expression pattern. Although considered as ion channels for almost two decades, recent structural and functional analyses refuted this role. Intriguingly, while all paralogs shared a dimeric stoichiometry following detergent solubilization, their structures revealed divergence in their relative subunit orientation. Here, we determined the stoichiometry of intact mouse TTYH (mTTYH) complexes in cells. Using cross-linking and single-molecule fluorescence microscopy, we demonstrate that mTTYH1 and mTTYH3 form tetramers at the plasma membrane, stabilized by interactions between their extracellular domains. Using blue-native PAGE, fluorescence-detection size-exclusion chromatography and hydrogen-deuterium exchange mass spectrometry (HDX-MS), we reveal that detergent solubilization results in tetramers destabilization, leading to their dissolution into dimers. Moreover, HDX-MS demonstrates that the extracellular domains are stabilized in the context of the tetrameric mTTYH complex. Together, our results expose the innate tetrameric organization of TTYH complexes at the cell membrane. Future structural analyses of these assemblies in native membranes are required to illuminate their long-sought cellular function.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:55:49.615.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPetr Man
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListN-glycosylated residue; acetylated residue; glycosylated residue
InstrumenttimsTOF Pro; Bruker Daltonics solarix series
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-02-22 13:07:07ID requested
12022-08-31 08:02:40announced
22023-11-14 08:55:50announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Tweety homolog family, TTYH, dimer, tetramer, hydrogen/deuterium exchange
Contact List
Petr Man
contact affiliationPetr Man, PhD Laboratory of Structural Biology and Cell Signaling BioCeV - Institute of Microbiology of the Czech Acad Sci Prumyslova 595 252 50 Vestec Czech Republic
contact emailpman@biomed.cas.cz
lab head
Petr Man
contact affiliationInstitute of Microbiology of the CAS
contact emailpman@biomed.cas.cz
dataset submitter
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Dataset FTP location
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