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Dev Cell. 2014 Jan 13;28(1):19-29. doi: 10.1016/j.devcel.2013.11.012. Epub 2013 Dec 19.

Structural insights into assembly and regulation of the plasma membrane phosphatidylinositol 4-kinase complex.

Author information

1
Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520, USA.
2
Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520, USA; Program in Cellular Neuroscience, Neurodegeneration, and Repair and Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06510, USA.
3
Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: karin.reinisch@yale.edu.

Abstract

Plasma membrane PI4P helps determine the identity of this membrane and plays a key role in signal transduction as the precursor of PI(4,5)P2 and its metabolites. Here, we report the atomic structure of the protein scaffold that is required for the plasma membrane localization and function of Stt4/PI4KIIIα, the PI 4-kinase responsible for this PI4P pool. Both proteins of the scaffold, Efr3 and YPP1/TTC7, are composed of α-helical repeats, which are arranged into a rod in Efr3 and a superhelix in Ypp1. A conserved basic patch in Efr3, which binds acidic phospholipids, anchors the complex to the plasma membrane. Stt4/PI4KIIIα is recruited by interacting with the Ypp1 C-terminal lobe, which also binds to unstructured regions in the Efr3 C terminus. Phosphorylation of this Efr3 region counteracts Ypp1 binding, thus providing a mechanism through which Stt4/PI4KIIIα recruitment, and thus a metabolic reaction of fundamental importance in cell physiology, can be regulated.

PMID:
24360784
PMCID:
PMC4349574
DOI:
10.1016/j.devcel.2013.11.012
[Indexed for MEDLINE]
Free PMC Article

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