Talk abstracts
Talk on Tuesday 03:00-03:15pm submitted by Anthony Rish
Cryogenic Electron Microscopy Structure of an Aminopeptidase Reveals a Mechanism of Cooperative Assembly
Anthony Rish (OSBP), Tian-Min Fu (Department of Biological Chemistry and Pharmacology, Comprehensive Cancer Center, The Ohio State University)
Abstract:
Aminopeptidases are widely distributed in all kingdoms of life and play important roles in many physiological processes via cleaving amino acids from the amino terminus of proteins. The assembly of aminopeptidases is critical for their function and is quite diverse from species to species. Here, we present the cryogenic electron microscopy (cryo-EM) structure of B. subtilis aminopeptidase at 3.8 Å resolution. The aminopeptidase assembles into a dodecamer consisting of four trimers, in which each protomer is composed of seven alpha-helices and 15 beta-strands and the 12 protomers interact with each other via establishing two different types of interfaces: a dimeric interface and a trimeric interface. Unexpectedly, mutations of key residues in these two interfaces completely disrupt the oligomerization of the aminopeptidase, suggesting a cooperative assembly of B. subtilis aminopeptidase mediated by both the dimeric interface and the trimeric interface. Adopting these results, protein design techniques may be able to leverage the cooperative effects of interface interactions as a potential avenue for generating novel therapeutics.
Keywords: Cryo-EM, Aminopeptidase, Cooperative Assembly