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TitleArchitecture of the human PI4KIIIα lipid kinase complex.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 114, Issue 52, Page 13720-13725, Year 2017
Publish dateDec 26, 2017
AuthorsJoshua A Lees / Yixiao Zhang / Michael S Oh / Curtis M Schauder / Xiaoling Yu / Jeremy M Baskin / Kerry Dobbs / Luigi D Notarangelo / Pietro De Camilli / Thomas Walz / Karin M Reinisch /
PubMed AbstractPlasma 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 ...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.
External linksProc Natl Acad Sci U S A / PubMed:29229838 / PubMed Central
MethodsEM (single particle)
Resolution3.6 Å
Structure data

EMDB-7129, PDB-6bq1:
Human PI4KIIIa lipid kinase complex
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-E4S:
5-{2-amino-1-[4-(morpholin-4-yl)phenyl]-1H-benzimidazol-6-yl}-N-(2-fluorophenyl)-2-methoxypyridine-3-sulfonamide

Source
  • homo sapiens (human)
KeywordsTransferase/Signaling Protein / kinase / phosphoinositide synthesis / Transferase-Signaling Protein complex

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