4GY2

Crystal structure of apo-Ia-actin complex

4GY2 の概要

• エントリーDOI: 10.2210/pdb4gy2/pdb
• 関連するPDBエントリー: 1GIQ 1GIR 3BUZ 4H03 4H0T 4H0V 4H0X 4H0Y
• 分子名称: Iota toxin component Ia, Actin, alpha skeletal muscle, PHOSPHATE ION, ... (7 entities in total)
• 機能のキーワード: adp-ribosyltransferase, toxin-structural protein complex, toxin/structural protein
• 由来する生物種: Clostridium perfringens; 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton: P68135
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 91145.57

構造登録者

Tsurumura, T.,Oda, M.,Nagahama, M.,Tsuge, H. (登録日: 2012-09-05, 公開日: 2013-02-20, 最終更新日: 2023-11-08)

主引用文献

Tsurumura, T.,Tsumori, Y.,Qiu, H.,Oda, M.,Sakurai, J.,Nagahama, M.,Tsuge, H.
Arginine ADP-ribosylation mechanism based on structural snapshots of iota-toxin and actin complex
Proc.Natl.Acad.Sci.USA, 110:4267-4272, 2013

PubMed Abstract: Clostridium perfringens iota-toxin (Ia) mono-ADP ribosylates Arg177 of actin, leading to cytoskeletal disorganization and cell death. To fully understand the reaction mechanism of arginine-specific mono-ADP ribosyl transferase, the structure of the toxin-substrate protein complex must be characterized. Recently, we solved the crystal structure of Ia in complex with actin and the nonhydrolyzable NAD(+) analog βTAD (thiazole-4-carboxamide adenine dinucleotide); however, the structures of the NAD(+)-bound form (NAD(+)-Ia-actin) and the ADP ribosylated form [Ia-ADP ribosylated (ADPR)-actin] remain unclear. Accidentally, we found that ethylene glycol as cryo-protectant inhibits ADP ribosylation and crystallized the NAD(+)-Ia-actin complex. Here we report high-resolution structures of NAD(+)-Ia-actin and Ia-ADPR-actin obtained by soaking apo-Ia-actin crystal with NAD(+) under different conditions. The structures of NAD(+)-Ia-actin and Ia-ADPR-actin represent the pre- and postreaction states, respectively. By assigning the βTAD-Ia-actin structure to the transition state, the strain-alleviation model of ADP ribosylation, which we proposed previously, is experimentally confirmed and improved. Moreover, this reaction mechanism appears to be applicable not only to Ia but also to other ADP ribosyltransferases.

PubMed: 23382240
DOI: 10.1073/pnas.1217227110

実験手法

X-RAY DIFFRACTION (2.71 Å)