title: The crystal structure of the phosphatidylinositol 4-kinase IIα.
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.
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, Prague, Czech Republic.
authors.forename: Adriana
authors.initials: A
authors.lastname: Baumlova
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, Prague, Czech Republic.
authors.forename: Dominika
authors.initials: D
authors.lastname: Chalupska
authors.affiliation: Institute of Physics Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Róźycki
authors.affiliation: Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD NIH, Bethesda, MD, USA.
authors.forename: Marko
authors.initials: M
authors.lastname: Jovic
authors.affiliation: Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD NIH, Bethesda, MD, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Wisniewski
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Klima
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, Prague, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Dubankova
authors.affiliation: Syngenta Jealott's Hill Internation Research Centre, Bracknell, UK.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Kloer
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, Prague, Czech Republic.
authors.forename: Radim
authors.initials: R
authors.lastname: Nencka
authors.affiliation: Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD NIH, Bethesda, MD, USA.
authors.forename: Tamas
authors.initials: T
authors.lastname: Balla
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR, Prague, Czech Republic boura@uochb.cas.cz.
authors.forename: Evzen
authors.initials: E
authors.lastname: Boura
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D007294:Inositol / Q000737:chemistry; D008566:Membranes / Q000737:chemistry; D015778:Minor Histocompatibility Antigens; D009010:Monte Carlo Method; D010716:Phosphatidylinositols / Q000737:chemistry / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D011487:Protein Conformation; D015398:Signal Transduction
chemical_list: D015778:Minor Histocompatibility Antigens; D010716:Phosphatidylinositols; D007294:Inositol; D017853:Phosphotransferases (Alcohol Group Acceptor); C402182:phosphatidylinositol phosphate 4-kinase
keywords: Monte Carlo simulations; crystal structure; kinase; membrane; phosphatidyl inositol