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The crystal structure of the phosphatidylinositol 4-kinase II?.

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 II? (PI4K II?), 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 II? recruitment, regulation, and function at the membrane.

SUBMITTER: Baumlova A

PROVIDER: S-EPMC4253849 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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The crystal structure of the phosphatidylinositol 4-kinase IIα.

Baumlova Adriana A Chalupska Dominika D Róźycki Bartosz B Jovic Marko M Wisniewski Eva E Klima Martin M Dubankova Anna A Kloer Daniel P DP Nencka Radim R Balla Tamas T Boura Evzen E

EMBO reports 20140828 10

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 late ...[more]

PMID: 25168678

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