Filament structures unveil the dynamic organization of human acetyl-CoA carboxylase

作者：Fayang Zhou, Yuanyuan Zhang, Yuyao Zhu, Qiang Zhou, Yigong Shi, Qi Hu · 发表于：Science Advances · 年份：2024 · DOI：10.1126/sciadv.ado4880 · 被引用次数：27 · 研究领域：Biotin and Related Studies、Microbial Metabolic Engineering and Bioproduction、Enzyme Structure and Function

Human acetyl-coenzyme A (CoA) carboxylases (ACCs) catalyze the carboxylation of acetyl-CoA, which is the rate-limiting step in fatty acid synthesis. The molecular mechanism underlying the dynamic organization of ACCs is largely unknown. Here, we determined the cryo-electron microscopy (EM) structure of human ACC1 in its inactive state, which forms a unique filament structure and is in complex with acetyl-CoA. We also determined the cryo-EM structure of human ACC1 activated by dephosphorylation and citrate treatment, at a resolution of 2.55 Å. Notably, the covalently linked biotin binds to a site that is distant from the acetyl-CoA binding site when acetyl-CoA is absent, suggesting a potential coordination between biotin binding and acetyl-CoA binding. These findings provide insights into the structural dynamics and regulatory mechanisms of human ACCs.