The crystal structure of PI4 kinase

Phosphatidylinositol 4-kinases (PI4K/PI4-kinases) catalyse the production of phosphatidylinositol 4-phosphate (PtdIns4P), the first step in the generation of higher phosphoinositides. PtdIns4P is an essential precursor in the production of second messengers, Ins(1,4,5)P3 and diacylglycerol, in a receptor activated phospholipase C signalling pathway. Moreover, PtdIns4P itself regulates conserved compartment-specific biological processes, mainly via recruiting a broad spectra of effector proteins. Because PI4-kinases have a central position in PtdIns4P synthesis on a surface of intracellular membranes, they are implicated in a wide range of PtdIns4P-induced processes such as lipid transport and metabolism, intracellular trafficking processes and cargo sorting, membrane and cytoskeleton remodelling events, signal transduction and many others. In mammals, two types of PI4-kinases were identified: type II and type III. Both types do not bear high sequence similarity to each other and, therefore, they possess diverse biochemical properties. In order to elucidate their structural relationship to other lipid kinases, structural analysis is highly demanded. The structural characterisation of individual PI4-kinases could also clarify the catalytic mechanism of PtdIns4P synthesis. Furthermore, information..