Klima Martin, Tóth Dániel J, Hexnerova Rozalie, Baumlova Adriana, Chalupska Dominika, Tykvart Jan, Rezabkova Lenka, Sengupta Nivedita, Man Petr, Dubankova Anna, Humpolickova Jana, Nencka Radim, Veverka Vaclav, Balla Tamas, Boura Evzen
Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2., 16610 Prague 6, Czech Republic.
Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD, NIH, Bethesda, MD 20892, USA.
Sci Rep. 2016 Mar 24;6:23641. doi: 10.1038/srep23641.
Phosphatidylinositol 4-kinase beta (PI4KB) is one of four human PI4K enzymes that generate phosphatidylinositol 4-phosphate (PI4P), a minor but essential regulatory lipid found in all eukaryotic cells. To convert their lipid substrates, PI4Ks must be recruited to the correct membrane compartment. PI4KB is critical for the maintenance of the Golgi and trans Golgi network (TGN) PI4P pools, however, the actual targeting mechanism of PI4KB to the Golgi and TGN membranes is unknown. Here, we present an NMR structure of the complex of PI4KB and its interacting partner, Golgi adaptor protein acyl-coenzyme A binding domain containing protein 3 (ACBD3). We show that ACBD3 is capable of recruiting PI4KB to membranes both in vitro and in vivo, and that membrane recruitment of PI4KB by ACBD3 increases its enzymatic activity and that the ACBD3:PI4KB complex formation is essential for proper function of the Golgi.
磷脂酰肌醇4-激酶β（PI4KB）是四种人类PI4K酶之一，可生成磷脂酰肌醇4-磷酸（PI4P），这是一种在所有真核细胞中都存在的少量但必不可少的调节性脂质。为了转化其脂质底物，PI4K必须被招募到正确的膜区室。PI4KB对于维持高尔基体和反式高尔基体网络（TGN）中的PI4P池至关重要，然而，PI4KB靶向高尔基体和TGN膜的实际机制尚不清楚。在这里，我们展示了PI4KB与其相互作用伙伴、含高尔基体衔接蛋白酰基辅酶A结合结构域蛋白3（ACBD3）的复合物的核磁共振结构。我们表明，ACBD3在体外和体内都能够将PI4KB招募到膜上，并且ACBD3对PI4KB的膜招募增加了其酶活性，而且ACBD3:PI4KB复合物的形成对于高尔基体的正常功能至关重要。
