6VP9

Cryo-EM structure of human NatB complex

6VP9 の概要

• エントリーDOI: 10.2210/pdb6vp9/pdb
• EMDBエントリー: 21307
• 分子名称: N-alpha-acetyltransferase 20, N-alpha-acetyltransferase 25, NatB auxiliary subunit, MDVFM peptide, ... (4 entities in total)
• 機能のキーワード: natb, naa20, naa25, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 132605.80

構造登録者

Deng, S.,Marmorstein, R. (登録日: 2020-02-02, 公開日: 2020-09-23, 最終更新日: 2024-03-06)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.46 Å)