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Publication Abstract from PubMed

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)P2 and PI(3,4,5)P3 This conversion is catalyzed by the PI4KIIIalpha complex, comprising a lipid kinase, PI4KIIIalpha, and two regulatory subunits, TTC7 and FAM126. We here report the structure of this complex at 3.6-A resolution, determined by cryo-electron microscopy. The proteins form an obligate approximately 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.

Architecture of the human PI4KIIIalpha lipid kinase complex.,Lees JA, Zhang Y, Oh MS, Schauder CM, Yu X, Baskin JM, Dobbs K, Notarangelo LD, De Camilli P, Walz T, Reinisch KM Proc Natl Acad Sci U S A. 2017 Dec 11. pii: 1718471115. doi:, 10.1073/pnas.1718471115. PMID:29229838^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.