Structural highlights
Function
[P4K2A_HUMAN] Together with PI4K2B and the type III PI4Ks (PIK4CA and PIK4CB) it contributes to the overall PI4-kinase activity of the cell. The phosphorylation of phosphatidylinositol (PI) to PI4P is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3). Contributes to the production of InsP3 in stimulated cells (By similarity). This lipid kinase is the major phosphatidylinositol 4-phosphate (PI4P) producer in the Golgi apparatus, it generates more than 50% of this molecule which is essential for the identity of the organelle, protein sorting and membrane trafficking.
Publication Abstract from PubMed
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 IIalpha (PI4K IIalpha), in complex with ATP solved by X-ray crystallography at 2.8 A 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 IIalpha recruitment, regulation, and function at the membrane.
The crystal structure of the phosphatidylinositol 4-kinase IIalpha,Baumlova A, Chalupska D, Rozycki B, Jovic M, Wisniewski E, Klima M, Dubankova A, Kloer DP, Nencka R, Balla T, Boura E EMBO Rep. 2014 Aug 28. pii: e201438841. PMID:25168678[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Baumlova A, Chalupska D, Rozycki B, Jovic M, Wisniewski E, Klima M, Dubankova A, Kloer DP, Nencka R, Balla T, Boura E. The crystal structure of the phosphatidylinositol 4-kinase IIalpha EMBO Rep. 2014 Aug 28. pii: e201438841. PMID:25168678 doi:http://dx.doi.org/10.15252/embr.201438841
