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The crystal structure of the phosphatidylinositol 4‐kinase II α
Author(s) -
Baumlova Adriana,
Chalupska Dominika,
Róźycki Bartosz,
Jovic Marko,
Wisniewski Eva,
Klima Martin,
Dubankova Anna,
Kloer Daniel P,
Nencka Radim,
Balla Tamas,
Boura Evzen
Publication year - 2014
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201438841
Subject(s) - phosphatidylinositol , kinase , mutagenesis , microbiology and biotechnology , biochemistry , function (biology) , biology , chemistry , biophysics , mutation , gene
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 α ( PI 4K II α), 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 PI 4K II α recruitment, regulation, and function at the membrane.