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  • 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 alpha (PI4K II alpha), in complex with ATP solved by X-ray crystallography at 2.8 angstrom resolution. The structure revealed a non-typical kinase fold that could be divided into Nand 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 alpha recruitment, regulation, and function at the membrane.
  • 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 alpha (PI4K II alpha), in complex with ATP solved by X-ray crystallography at 2.8 angstrom resolution. The structure revealed a non-typical kinase fold that could be divided into Nand 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 alpha recruitment, regulation, and function at the membrane. (en)
Title
  • The crystal structure of the phosphatidylinositol 4-kinase II alpha
  • The crystal structure of the phosphatidylinositol 4-kinase II alpha (en)
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  • The crystal structure of the phosphatidylinositol 4-kinase II alpha
  • The crystal structure of the phosphatidylinositol 4-kinase II alpha (en)
skos:notation
  • RIV/61388963:_____/14:00435136!RIV15-AV0-61388963
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  • 9296
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  • RIV/61388963:_____/14:00435136
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  • crystal structure; kinase; membrane; Monte Carlo simulations; phosphatidyl inositol (en)
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  • 15
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  • Nencka, Radim
  • Bouřa, Evžen
  • Klíma, Martin
  • Balla, T.
  • Rozycki, B.
  • Chalupská, Dominika
  • Bäumlová, Adriana
  • Dubánková, Anna
  • Jovic, M.
  • Kloer, D. P.
  • Wisniewski, E.
http://linked.open...ain/vavai/riv/wos
  • 000342890700012
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  • 1469-221X
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http://bibframe.org/vocab/doi
  • 10.15252/embr.201438841
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