6VP9

Cryo-EM structure of human NatB complex

Summary for 6VP9

• Entry DOI: 10.2210/pdb6vp9/pdb
• EMDB information: 21307
• Descriptor: N-alpha-acetyltransferase 20, N-alpha-acetyltransferase 25, NatB auxiliary subunit, MDVFM peptide, ... (4 entities in total)
• Functional Keywords: natb, naa20, naa25, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 132605.80

Authors

Deng, S.,Marmorstein, R. (deposition date: 2020-02-02, release date: 2020-09-23, Last modification date: 2024-03-06)

Primary citation

Deng, S.,Pan, B.,Gottlieb, L.,Petersson, J.,Marmorstein, R.
Molecular basis for N-terminal alpha-synuclein acetylation by human NatB.
Elife, 9:-, 2020

PubMed Abstract: NatB is one of three major N-terminal acetyltransferase (NAT) complexes (NatA-NatC), which co-translationally acetylate the N-termini of eukaryotic proteins. Its substrates account for about 21% of the human proteome, including well known proteins such as actin, tropomyosin, CDK2, and α-synuclein (αSyn). Human NatB (hNatB) mediated N-terminal acetylation of αSyn has been demonstrated to play key roles in the pathogenesis of Parkinson's disease and as a potential therapeutic target for hepatocellular carcinoma. Here we report the cryo-EM structure of hNatB bound to a CoA-αSyn conjugate, together with structure-guided analysis of mutational effects on catalysis. This analysis reveals functionally important differences with human NatA and NatB, resolves key hNatB protein determinants for αSyn N-terminal acetylation, and identifies important residues for substrate-specific recognition and acetylation by NatB enzymes. These studies have implications for developing small molecule NatB probes and for understanding the mode of substrate selection by NAT enzymes.

PubMed: 32885784
DOI: 10.7554/eLife.57491

Experimental method

ELECTRON MICROSCOPY (3.46 Å)