9BAX
PI4KA complex bound to C-terminus of EFR3A
Summary for 9BAX
| Entry DOI | 10.2210/pdb9bax/pdb |
| EMDB information | 44413 |
| Descriptor | Protein EFR3 homolog A, Phosphatidylinositol 4-kinase alpha, Tetratricopeptide repeat protein 7B, ... (4 entities in total) |
| Functional Keywords | pi4ka, ttc7b, fam126a, efr3a, efr3, lipid signaling, pi4kiiia, phosphoinositide kinase, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 8 |
| Total formula weight | 760804.24 |
| Authors | Shaw, A.L.,Suresh, S.,Yip, C.K.,Burke, J.E. (deposition date: 2024-04-04, release date: 2024-11-27, Last modification date: 2025-02-12) |
| Primary citation | Suresh, S.,Shaw, A.L.,Pemberton, J.G.,Scott, M.K.,Harris, N.J.,Parson, M.A.H.,Jenkins, M.L.,Rohilla, P.,Alvarez-Prats, A.,Balla, T.,Yip, C.K.,Burke, J.E. Molecular basis for plasma membrane recruitment of PI4KA by EFR3. Sci Adv, 10:eadp6660-eadp6660, 2024 Cited by PubMed Abstract: The lipid kinase phosphatidylinositol 4 kinase III α (PI4KIIIα/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. Fundamental to PI4KA activity is its targeted recruitment to the plasma membrane by the lipidated proteins EFR3A and EFR3B. Here, we report a cryogenic electron microscopy structure of the C terminus of EFR3A bound to the PI4KA-TTC7B-FAM126A complex, with extensive validation using both hydrogen deuterium exchange mass spectrometry, and mutational analysis. The EFR3A C terminus undergoes a disorder-order transition upon binding to the PI4KA complex, with an unexpected direct interaction with both TTC7B and FAM126A. Complex disrupting mutations in TTC7B, FAM126A, and EFR3 decrease PI4KA recruitment to the plasma membrane. Multiple posttranslational modifications and disease linked mutations map to this site, providing insight into how PI4KA membrane recruitment can be regulated and disrupted in human disease. PubMed: 39705356DOI: 10.1126/sciadv.adp6660 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.65 Å) |
Structure validation
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