Decoding allosteric regulation by the acyl carrier protein
Terra Sztain, Thomas G. Bartholow, D. John Lee, Lorenzo Casalino, Andrew R. Mitchell, Megan A. Young, Jia‐Ning Wang, J. Andrew McCammon, Michael D. Burkart
Abstract
Significance Acyl carrier proteins (ACPs) are involved in primary and secondary metabolic pathways, including the ubiquitous fatty acid biosynthesis, required for all domains of life. This single protein must deliver pathway intermediates to the appropriate enzyme, distinguishing between a myriad of possible intermediate-enzyme combinations. The intermediate is delivered to the active site of enzymes through a large conformational change termed “chain flipping.” Whether chain flipping is a stochastic or regulated process has remained a mystery. This study provides evidence for an allosteric regulatory mechanism—demonstrating that substrates sequestered within the interior side of the four-helical ACP bundle confer structural changes to the exterior which are recognized by enzymes via protein–protein interactions—presenting a unique paradigm for understanding these biosynthetic pathways.