2. Academic Validation
  3. The crystal structure of the phosphatidylinositol 4-kinase IIα

The crystal structure of the phosphatidylinositol 4-kinase IIα

  • EMBO Rep. 2014 Oct;15(10):1085-92. doi: 10.15252/embr.201438841.
Adriana Baumlova 1,  Dominika Chalupska 1,  Bartosz Róźycki 2,  Marko Jovic 3,  Eva Wisniewski 3,  Martin Klima 1,  Anna Dubankova 1,  Daniel P Kloer 4,  Radim Nencka 1,  Tamas Balla 3,  Evzen Boura 5
Affiliations

Affiliations

  • 1 Institute of Organic Chemistry and Biochemistry AS CR, Prague, Czech Republic.
  • 2 Institute of Physics Polish Academy of Sciences, Warsaw, Poland.
  • 3 Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD NIH, Bethesda, MD, USA.
  • 4 Syngenta Jealott's Hill Internation Research Centre, Bracknell, UK.
  • 5 Institute of Organic Chemistry and Biochemistry AS CR, Prague, Czech Republic boura@uochb.cas.cz.
PMID: 25168678 DOI: 10.15252/embr.201438841
Abstract

Phosphoinositides are a class of Phospholipids generated by the action of phosphoinositide kinases with key regulatory functions in eukaryotic cells. Here, we present the atomic structure of phosphatidylinositol 4-kinase type IIα (PI4K IIα), in complex with ATP solved by X-ray crystallography at 2.8 Å resolution. The structure revealed a non-typical kinase fold that could be divided into N- and C-lobes with the ATP binding groove located in between. Surprisingly, a second ATP was found in a lateral hydrophobic pocket of the C-lobe. Molecular simulations and mutagenesis analysis revealed the membrane binding mode and the putative function of the hydrophobic pocket. Taken together, our results suggest a mechanism of PI4K IIα recruitment, regulation, and function at the membrane.

Keywords

Monte Carlo simulations; crystal structure; kinase; membrane; phosphatidyl inositol.

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