Molecular mechanism of N-terminal acetylation by the ternary NatC complex

• DOI: 10.1016/j.str.2021.05.003
• Publication Date: 2021-05-20T14:56:08Z
• Authors: Sunbin Deng; Leah Gottlieb; Buyan Pan; Julianna Supplee; Xuepeng Wei; E James Petersson; Ronen Marmorstein
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences; Binding Sites; Phytic Acid; Schizosaccharomyces; Acetylation; Schizosaccharomyces pombe Proteins; Protein Multimerization; Protein Binding

AbstractProtein N-terminal acetylation is predominantly a ribosome-associated modification, with NatA-E serving as the major enzymes. NatC is the most unusual of these enzymes, containing one Naa30 catalytic subunit and two auxiliary subunits, Naa35 and Naa38; and substrate specificity profile that overlaps with NatE. Here, we report the Cryo-EM structure ofS. pombeNatC with a NatE/C-type bisubstrate analogue and inositol hexaphosphate (IP6), and associated biochemistry studies. We find that the presence of three subunits is a prerequisite for normal NatC acetylation activity in yeast and that IP6binds tightly to NatC to stabilize the complex. We also describe the molecular basis for IP6-mediated NatC complex stabilization and the overlapping yet distinct substrate profiles of NatC and NatE.