Architecture of the human PI4KIIIα lipid kinase complex.
Proc Natl Acad Sci U S A
; 114(52): 13720-13725, 2017 12 26.
Article
em En
| MEDLINE
| ID: mdl-29229838
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)P2 and PI(3,4,5)P3 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 â¼700-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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas
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Modelos Moleculares
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Fosfatos de Fosfatidilinositol
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Fosfatidilinositol 4,5-Difosfato
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1-Fosfatidilinositol 4-Quinase
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Complexos Multiproteicos
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Peptídeos e Proteínas de Sinalização Intracelular
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Proteínas de Membrana
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2017
Tipo de documento:
Article