PXD066213

PXD066213 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	HDX-MS analysis of a TTC7B specific nanobody to inhibit EFR3 mediated PI4KA recruitment
Description	Phosphatidylinositol 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.
HostingRepository	PRIDE
AnnounceDate	2025-11-20
AnnouncementXML	Submission_2025-11-20_12:20:10.226.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	John Burke
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 120

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-16 07:18:21	ID requested
⏵ 1	2025-11-20 12:20:11	announced

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;

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

submitter keyword: PI4KA, HDX-MS, nanaobody, TTC7B

Contact List

John E Burke
contact affiliation	University of Victoria
contact email	jeburke@uvic.ca
lab head
John Burke
contact affiliation	University of Victoria
contact email	jeburke@uvic.ca
dataset submitter

Full Dataset Link List

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/2025/11/PXD066213
PRIDE project URI

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/2025/11/PXD066213

PRIDE project URI

Repository Record List

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