7S0Y

Structures of TcdB in complex with Cdc42

7S0Y の概要

• エントリーDOI: 10.2210/pdb7s0y/pdb
• 分子名称: Toxin B, Cell division control protein 42 homolog, MANGANESE (II) ION, ... (8 entities in total)
• 機能のキーワード: toxin, substrate, enzyme, hydrolase
• 由来する生物種: Clostridioides difficile (Peptoclostridium difficile); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 84920.53

構造登録者

Zheng, L.,Rongsheng, J.,Peng, C. (登録日: 2021-08-31, 公開日: 2021-09-08, 最終更新日: 2023-10-18)

主引用文献

Liu, Z.,Zhang, S.,Chen, P.,Tian, S.,Zeng, J.,Perry, K.,Dong, M.,Jin, R.
Structural basis for selective modification of Rho and Ras GTPases by Clostridioides difficile toxin B.
Sci Adv, 7:eabi4582-eabi4582, 2021

PubMed Abstract: Toxin B (TcdB) is a primary cause of infection (CDI). This toxin acts by glucosylating small GTPases in the Rho/Ras families, but the structural basis for TcdB recognition and selectivity of specific GTPase substrates remain unsolved. Here, we report the cocrystal structures of the glucosyltransferase domain (GTD) of two distinct TcdB variants in complex with human Cdc42 and R-Ras, respectively. These structures reveal a common structural mechanism by which TcdB recognizes Rho and R-Ras. Furthermore, we find selective clustering of adaptive residue changes in GTDs that determine their substrate preferences, which helps partition all known TcdB variants into two groups that display distinct specificities toward Rho or R-Ras. Mutations that selectively disrupt GTPases binding reduce the glucosyltransferase activity of the GTD and the toxicity of TcdB holotoxin. These findings establish the structural basis for TcdB recognition of small GTPases and reveal strategies for therapeutic interventions for CDI.

PubMed: 34678063
DOI: 10.1126/sciadv.abi4582

実験手法

X-RAY DIFFRACTION (2.79 Å)