Abstract 2322 Molecular basis for the regulation of PI4KA at the plasma membrane
The lipid kinase phosphatidylinositol 4 kinase III alpha (PI4KIIIa/PI4KA) is a master regulator of the lipid composition and asymmetry of the plasma membrane. PI4KA exists primarily in a heterotrimeric complex with its regulatory proteins TTC7 and FAM126. Additonally, PI4KA is regulated by a number of regulatory proteins (1,2). Fundamental to PI4KA activity is its targeted recruitment to the plasma membrane by the lipidated proteins EFR3A and EFR3B. Here, we determined a cryo-EM structure of the C-terminus of EFR3A bound to the PI4KA-TTC7B-FAM126A complex, with extensive validation using both hydrogen deuterium exchange mass spectrometry (HDX-MS), and mutational analysis.
Authors
- Sushant Suresh (ORCID: https://orcid.org/0009-0005-7220-7339)
- Meredith L. Jenkins (ORCID: https://orcid.org/0000-0002-0685-5048)
- Matthew Parson
- Joshua G. Pemberton (ORCID: https://orcid.org/0000-0002-1492-1471)
- Calvin K. Yip (ORCID: https://orcid.org/0000-0003-1779-9501)
- Tamás Balla (ORCID: https://orcid.org/0000-0002-9077-3335)
- Alexandria Shaw
- John E. Burke (ORCID: https://orcid.org/0000-0001-7904-9859)
- Mackenzie Scott
Institutions
- Victoria University (AU)
Publication Details
- Journal
- Journal of Biological Chemistry
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1016/j.jbc.2025.109982
- Primary Topic
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Natural Sciences and Engineering Research Council of Canada
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development