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-Structure paper
Title | Molecular basis for N-terminal alpha-synuclein acetylation by human NatB. |
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Journal, issue, pages | Elife, Vol. 9, Year 2020 |
Publish date | Sep 4, 2020 |
Authors | Sunbin Deng / Buyan Pan / Leah Gottlieb / E James Petersson / Ronen Marmorstein / |
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 ...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. |
External links | Elife / PubMed:32885784 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.46 Å |
Structure data | EMDB-21307, PDB-6vp9: |
Chemicals | ChemComp-CMC: |
Source |
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Keywords | TRANSFERASE / NatB / NAA20 / NAA25 |