7MX2

Cryo-EM structure of human ternary NatC complex with a Bisubstrate inhibitor

Summary for 7MX2

• Entry DOI: 10.2210/pdb7mx2/pdb
• EMDB information: 24070
• Descriptor: N-alpha-acetyltransferase 35, NatC auxiliary subunit, N-alpha-acetyltransferase 38, NatC auxiliary subunit, N-alpha-acetyltransferase 30, ... (5 entities in total)
• Functional Keywords: natc, naa30, naa35, naa38, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 116609.71

Authors

Deng, S.,Marmorstein, R. (deposition date: 2021-05-18, release date: 2022-12-14, Last modification date: 2024-11-06)

Primary citation

Deng, S.,Gardner, S.M.,Gottlieb, L.,Pan, B.,Petersson, E.J.,Marmorstein, R.
Molecular role of NAA38 in thermostability and catalytic activity of the human NatC N-terminal acetyltransferase.
Structure, 31:166-173.e4, 2023

PubMed Abstract: N-terminal acetylation occurs on over 80% of human proteins and is catalyzed by a family of N-terminal acetyltransferases (NATs). All NATs contain a small catalytic subunit, while some also contain a large auxiliary subunit that facilitates catalysis and ribosome targeting for co-translational acetylation. NatC is one of the major NATs containing an NAA30 catalytic subunit, but uniquely contains two auxiliary subunits, large NAA35 and small NAA38. Here, we report the cryo-EM structures of human NatC (hNatC) complexes with and without NAA38, together with biochemical studies, to reveal that NAA38 increases the thermostability and broadens the substrate-specificity profile of NatC by ordering an N-terminal segment of NAA35 and reorienting an NAA30 N-terminal peptide binding loop for optimal catalysis, respectively. We also note important differences in engagement with a stabilizing inositol hexaphosphate molecule between human and yeast NatC. These studies provide new insights for the function and evolution of the NatC complex.

PubMed: 36638802
DOI: 10.1016/j.str.2022.12.008

Experimental method

ELECTRON MICROSCOPY (3.64 Å)