Trapping the dynamic acyl carrier protein in fatty acid biosynthesis

During fatty acid and polyketide biosynthesis the growing polymer chain is stabilized by acyl carrier proteins (ACPs), but the transient nature of the process makes it difficult to visualize the molecular mechanisms involved. Two papers published in this issue of Nature use strategies that circumvent this problem. Ali Masoudi et al. solve the X-ray crystal structures of an ACP from Escherichia coli bound to LpxD, an acyltransferase in the lipid A biosynthetic pathway, in three different states: an intact acyl-ACP, a hydrolysed-acyl-ACP, and a holo-ACP form. Alignment of these structures makes it possible to visualize the conformational changes that take place in the ACP during catalysis. Chi Nguyen et al. use a crosslinking probe to tether an ACP to an active site histidine of one of its catalytic enzymes, the dehydratase FabA from E. coli. They obtain a high-resolution X-ray crystal structure of the stabilized ACPFabA complex and use NMR spectroscopy to probe the dynamics of ACPFabA interactions. Their experiments support a 'switchblade' model. This crosslink-probe approach can be applied to other carrier protein partners in metabolic and signalling pathways.