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

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


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.

MeSH terms

  • 1-Phosphatidylinositol 4-Kinase / chemistry*
  • 1-Phosphatidylinositol 4-Kinase / genetics
  • 1-Phosphatidylinositol 4-Kinase / metabolism
  • Adaptor Proteins, Vesicular Transport / chemistry*
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Amino Acid Sequence
  • Binding Sites
  • Cell Membrane / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Phospholipids / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Transport
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism


  • Adaptor Proteins, Vesicular Transport
  • EFR3 protein, S cerevisiae
  • Phospholipids
  • Saccharomyces cerevisiae Proteins
  • YPP1 protein, S cerevisiae
  • 1-Phosphatidylinositol 4-Kinase
  • STT4 protein, S cerevisiae

Associated data

  • PDB/4N5A
  • PDB/4N5C