Structural Insights into the Regulation of ACC2 by Citrate

Bulletin of the Korean chemical society

Yong Soon Cho¹  Seong Jung Kwon¹  Yong-Seok Heo¹ 

关键词: Acetyl-CoA carboxylase;    Biotin carboxylase;    Phosphorylation;    Citrate;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

Acetyl-CoA carboxylases (ACCs) play critical roles in fatty acid synthesis and oxidation by the catalytic activity of the carboxylation of acetyl-CoA to malonyl-CoA. It is known that ACCs are inactivated through reversible phosphorylation by AMP-activated protein kinase (AMPK) and allosterically activated by citrate. Here, we determined the crystal structures of biotin carboxylase (BC) domain of human ACC2 phosphorylated by AMPK in the presence of citrate in order to elucidate the activation mechanism by citrate. This structure shows that phosphorylated Ser222 is released from the dimer interface, and thereby facilitating the dimerization or oligomerization of the BC domain allosterically. This structural explanation is coincident with the experimental result that the phosphorylated Ser222 was dephosphorylated more easily by protein phosphatase 2A (PP2A) as the citrate concentration increases.

【 授权许可】

Unknown