5WJD

Crystal structure of Naa80 bound to acetyl-CoA

5WJD の概要

• エントリーDOI: 10.2210/pdb5wjd/pdb
• 分子名称: CG8481, isoform B, ACETYL COENZYME *A, CITRIC ACID, ... (4 entities in total)
• 機能のキーワード: acetyltransferase, acetyl-coa, gnat fold, acetylation, transferase
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19128.97

構造登録者

Goris, M.,Magin, R.S.,Marmorstein, R.,Arnesen, T. (登録日: 2017-07-21, 公開日: 2018-03-28, 最終更新日: 2024-12-25)

主引用文献

Goris, M.,Magin, R.S.,Foyn, H.,Myklebust, L.M.,Varland, S.,Ree, R.,Drazic, A.,Bhambra, P.,Stove, S.I.,Baumann, M.,Haug, B.E.,Marmorstein, R.,Arnesen, T.
Structural determinants and cellular environment define processed actin as the sole substrate of the N-terminal acetyltransferase NAA80.
Proc. Natl. Acad. Sci. U.S.A., 115:4405-4410, 2018

PubMed Abstract: N-terminal (Nt) acetylation is a major protein modification catalyzed by N-terminal acetyltransferases (NATs). Methionine acidic N termini, including actin, are cotranslationally Nt acetylated by NatB in all eukaryotes, but animal actins containing acidic N termini, are additionally posttranslationally Nt acetylated by NAA80. Actin Nt acetylation was found to regulate cytoskeletal dynamics and motility, thus making NAA80 a potential target for cell migration regulation. In this work, we developed potent and selective bisubstrate inhibitors for NAA80 and determined the crystal structure of NAA80 in complex with such an inhibitor, revealing that NAA80 adopts a fold similar to other NAT enzymes but with a more open substrate binding region. Furthermore, in contrast to most other NATs, the substrate specificity of NAA80 is mainly derived through interactions between the enzyme and the acidic amino acids at positions 2 and 3 of the actin substrate and not residues 1 and 2. A yeast model revealed that ectopic expression of NAA80 in a strain lacking NatB activity partially restored Nt acetylation of NatB substrates, including yeast actin. Thus, NAA80 holds intrinsic capacity to posttranslationally Nt acetylate NatB-type substrates in vivo. In sum, the presence of a dominant cotranslational NatB in all eukaryotes, the specific posttranslational actin methionine removal in animals, and finally, the unique structural features of NAA80 leave only the processed actins as in vivo substrates of NAA80. Together, this study reveals the molecular and cellular basis of NAA80 Nt acetylation and provides a scaffold for development of inhibitors for the regulation of cytoskeletal properties.

PubMed: 29581307
DOI: 10.1073/pnas.1719251115

実験手法

X-RAY DIFFRACTION (2.001 Å)