6BQ1

Human PI4KIIIa lipid kinase complex

Summary for 6BQ1

• Entry DOI: 10.2210/pdb6bq1/pdb
• EMDB information: 7129
• Descriptor: Phosphatidylinositol 4-kinase III alpha (PI4KA), Tetratricopeptide repeat protein 7B, Protein FAM126A, ... (5 entities in total)
• Functional Keywords: kinase, phosphoinositide synthesis, transferase-signaling protein complex, transferase/signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 607175.40

Authors

Lees, J.A.,Zhang, Y.,Oh, M.,Schauder, C.M.,Yu, X.,Baskin, J.,Dobbs, K.,Notarangelo, L.D.,Camilli, P.D.,Walz, T.,Reinisch, K.M. (deposition date: 2017-11-27, release date: 2017-12-13, Last modification date: 2024-03-13)

Primary citation

Lees, J.A.,Zhang, Y.,Oh, M.S.,Schauder, C.M.,Yu, X.,Baskin, J.M.,Dobbs, K.,Notarangelo, L.D.,De Camilli, P.,Walz, T.,Reinisch, K.M.
Architecture of the human PI4KIII alpha lipid kinase complex.
Proc. Natl. Acad. Sci. U.S.A., 114:13720-13725, 2017

PubMed Abstract: Plasma membrane (PM) phosphoinositides play essential roles in cell physiology, serving as both markers of membrane identity and signaling molecules central to the cell's interaction with its environment. The first step in PM phosphoinositide synthesis is the conversion of phosphatidylinositol (PI) to PI4P, the precursor of PI(4,5)P and PI(3,4,5)P This conversion is catalyzed by the PI4KIIIα complex, comprising a lipid kinase, PI4KIIIα, and two regulatory subunits, TTC7 and FAM126. We here report the structure of this complex at 3.6-Å resolution, determined by cryo-electron microscopy. The proteins form an obligate ∼700-kDa superassembly with a broad surface suitable for membrane interaction, toward which the kinase active sites are oriented. The structural complexity of the assembly highlights PI4P synthesis as a major regulatory junction in PM phosphoinositide homeostasis. Our studies provide a framework for further exploring the mechanisms underlying PM phosphoinositide regulation.

PubMed: 29229838
DOI: 10.1073/pnas.1718471115

Experimental method

ELECTRON MICROSCOPY (3.6 Å)