2A9K

Crystal structure of the C3bot-NAD-RalA complex reveals a novel type of action of a bacterial exoenzyme

2A9K の概要

• エントリーDOI: 10.2210/pdb2a9k/pdb
• 関連するPDBエントリー: 1G24 1U8Z 1U90 1UAD 2A78 2BOV
• 分子名称: Ras-related protein Ral-A, Mono-ADP-ribosyltransferase C3, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: exoenzyme c3, bacterial adp-ribosyltransferase, ral, rho, gdp-binding, protein binding-transferase complex, protein binding/transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane ; Lipid- anchor ; Cytoplasmic side: P11233; Secreted: P15879
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46489.01

構造登録者

Pautsch, A.,Vogelsgesang, M.,Trankle, J.,Herrmann, C.,Aktories, K. (登録日: 2005-07-12, 公開日: 2005-10-11, 最終更新日: 2023-08-23)

主引用文献

Pautsch, A.,Vogelsgesang, M.,Trankle, J.,Herrmann, C.,Aktories, K.
Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme.
Embo J., 24:3670-3680, 2005

PubMed Abstract: C3 exoenzymes from bacterial pathogens ADP-ribosylate and inactivate low-molecular-mass GTPases of the Rho subfamily. Ral, a Ras subfamily GTPase, binds the C3 exoenzymes from Clostridium botulinum and C. limosum with high affinity without being a substrate for ADP ribosylation. In the complex, the ADP-ribosyltransferase activity of C3 is blocked, while binding of NAD and NAD-glycohydrolase activity remain. Here we report the crystal structure of C3 from C. botulinum in a complex with GDP-bound RalA at 1.8 A resolution. C3 binds RalA with a helix-loop-helix motif that is adjacent to the active site. A quaternary complex with NAD suggests a mode for ADP-ribosyltransferase inhibition. Interaction of C3 with RalA occurs at a unique interface formed by the switch-II region, helix alpha3 and the P loop of the GTPase. C3-binding stabilizes the GDP-bound conformation of RalA and blocks nucleotide release. Our data indicate that C. botulinum exoenzyme C3 is a single-domain toxin with bifunctional properties targeting Rho GTPases by ADP ribosylation and Ral by a guanine nucleotide dissociation inhibitor-like effect, which blocks nucleotide exchange.

PubMed: 16177825
DOI: 10.1038/sj.emboj.7600813

実験手法

X-RAY DIFFRACTION (1.73 Å)