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

Sunbin Deng; Leah Gottlieb; Buyan Pan; Julianna Supplee; Xuepeng Wei; E James Petersson; Ronen Marmorstein

doi:10.1016/j.str.2021.05.003

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

Structure. 2021 Oct 7;29(10):1094-1104.e4. doi: 10.1016/j.str.2021.05.003. Epub 2021 May 20.

Authors

Sunbin Deng¹, Leah Gottlieb¹, Buyan Pan², Julianna Supplee³, Xuepeng Wei⁴, E James Petersson², Ronen Marmorstein⁵

Affiliations

¹ Department of Chemistry, 231 South 34(th) Street, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
² Department of Chemistry, 231 South 34(th) Street, University of Pennsylvania, Philadelphia, PA 19104, USA.
³ Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA; Graduate Group in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
⁴ Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
⁵ Department of Chemistry, 231 South 34(th) Street, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA. Electronic address: marmor@upenn.edu.

Abstract

Protein 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 selectivity profile that overlaps with NatE. Here, we report the cryoelectron microscopy structure of S. pombe NatC with a NatE/C-type bisubstrate analog 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 IP₆ binds 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.

Keywords: IP6; N-terminal acetylation; N-terminal acetyltransferase; NATs; NatC; co-translational modification; enzyme mechanism; ribosome.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Acetylation
Binding Sites
Phytic Acid / chemistry
Phytic Acid / metabolism
Protein Binding
Protein Multimerization
Schizosaccharomyces
Schizosaccharomyces pombe Proteins / chemistry*
Schizosaccharomyces pombe Proteins / metabolism

Substances

Schizosaccharomyces pombe Proteins
Phytic Acid

Abstract

Publication types

MeSH terms

Substances

Grants and funding