8xl2
From Proteopedia
Human acetyl-CoA carboxylase 1 filament in complex with acetyl-CoA (ACC1-inact)
Structural highlights
DiseaseACACA_HUMAN Defects in ACACA are a cause of acetyl-CoA carboxylase 1 deficiency (ACACAD) [MIM:613933; also known as ACAC deficiency or ACC deficiency. An inborn error of de novo fatty acid synthesis associated with severe brain damage, persistent myopathy and poor growth.[1] FunctionACACA_HUMAN Catalyzes the rate-limiting reaction in the biogenesis of long-chain fatty acids. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase.[2] Publication Abstract from PubMedHuman 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 A. 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. Filament structures unveil the dynamic organization of human acetyl-CoA carboxylase.,Zhou F, Zhang Y, Zhu Y, Zhou Q, Shi Y, Hu Q Sci Adv. 2024 Oct 11;10(41):eado4880. doi: 10.1126/sciadv.ado4880. Epub 2024 Oct , 9. PMID:39383219[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
Categories: Homo sapiens | Large Structures | Hu Q | Zhang YY | Zhou FY | Zhou Q
