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PXD066213-1

PXD066213 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHDX-MS analysis of a TTC7B specific nanobody to inhibit EFR3 mediated PI4KA recruitment
DescriptionPhosphatidylinositol 4 kinase III (PI4KIII/PI4KA) is an essential lipid kinase that is critical for regulating plasma membrane identity. PI4KA is primarily recruited to the plasma membrane through targeted recruitment by the proteins EFR3A and EFR3B, with these binding to the PI4KA accessory proteins TTC7 (TTC7A and TTC7B) and FAM126 (FAM126A and FAM126B). Here we characterised how both EFR3 isoforms interact with all possible TTC7 and FAM126 combinations and developed a nanobody that specifically blocks EFR3 mediated PI4KA recruitment in TTC7B containing complexes. Using a yeast display approach, we generated a nanobody that is selective for TTC7B and blocks EFR3 binding. Cryo-electron microscopy and hydrogen deuterium exchange mass spectrometry reveal that the nanobody sterically blocks EFR3 recruitment and shows an extended interface with both PI4KA and TTC7B. Overall, this work provides insight into PI4KA regulation and is a useful tool for manipulating unique complexes of PI4KA that may be valuable for future therapeutic targeting of PI4KA.
HostingRepositoryPRIDE
AnnounceDate2025-11-20
AnnouncementXMLSubmission_2025-11-20_12:20:10.226.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJohn Burke
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Exploris 120
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-07-16 07:18:21ID requested
12025-11-20 12:20:11announced
Publication List
Suresh S, Shaw AL, Akintola DK, Lunke M, Doerr S, Rohilla P, Balla T, Yip CK, Hansen SD, Cobb JA, Burke JE, Development of an inhibitory TTC7B selective nanobody that blocks EFR3 recruitment of PI4KA. J Biol Chem, 301(12):110886(2025) [pubmed]
10.1016/j.jbc.2025.110886;
Keyword List
submitter keyword: PI4KA, HDX-MS, nanaobody, TTC7B
Contact List
John E Burke
contact affiliationUniversity of Victoria
contact emailjeburke@uvic.ca
lab head
John Burke
contact affiliationUniversity of Victoria
contact emailjeburke@uvic.ca
dataset submitter
Full Dataset Link List
Dataset FTP location
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Repository Record List
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