Architecture of the human PI4KIIIα lipid kinase complex.
basic_science · Level V
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- Record sourced from PubMed, PMID 29229838.
- Also identified by DOI 10.1073/pnas.1718471115 and PMC identifier 5748228.
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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<sub>2</sub> and PI(3,4,5)P<sub>3</sub> 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.
Medical subject headings
- 1-Phosphatidylinositol 4-Kinase
- Intracellular Signaling Peptides and Proteins
- Membrane Proteins
- Models, Molecular
- Multiprotein Complexes
- Phosphatidylinositol 4,5-Diphosphate
- Phosphatidylinositol Phosphates
- Proteins