Crystal structure and calcium-induced conformational changes of diacylglycerol kinase α EF-hand domains.

ABSTRACT: Diacylglycerol kinases (DGKs) are multi-domain lipid kinases that phosphorylate diacylglycerol into phosphatidic acid, modulating the levels of these key signaling lipids. Recently, increasing attention has been paid to DGKα isozyme as a potential target for cancer immunotherapy. We have previously shown that DGKα is positively regulated by Ca²⁺ binding to its N-terminal EF-hand domains (DGKα-EF). However, little progress has been made for the structural biology of mammalian DGKs and the molecular mechanism underlying the Ca²⁺ -triggered activation remains unclear. Here we report the first crystal structure of Ca²⁺ -bound DGKα-EF and analyze the structural changes upon binding to Ca²⁺ . DGKα-EF adopts a canonical EF-hand fold, but unexpectedly, h

SUBMITTER: Takahashi D 

PROVIDER: S-EPMC6423725 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature