Active E. coli heteromeric acetyl-CoA carboxylase forms polymorphic helical tubular filaments

The Escherichia coli heteromeric acetyl-CoA carboxylase (ACC) has three functional subunits assumed to form an elusive catalytic complex and they are involved in allosteric and transcriptional regulation. The E. coli ACC represents almost all ACCs from pathogenic bacteria, making it a key antibiotic development target to fight growing antibiotic resistance. Furthermore, it is a model for cyanobacterial and plant plastid ACCs as biofuel engineering targets. Here, we report the catalytic E. coli ACC complex surprisingly forms tubes rather than dispersed particles. The cryo-EM structure reveals key protein-protein interactions underpinning efficient catalysis and how transcriptional regulatory roles are masked during catalysis. Discovering the protein-protein interaction interfaces that facilitate catalysis, allosteric, and transcriptional regulation provides new routes to engineering catalytic activity and new targets for drug discovery.