7S0Z

Structures of TcdB in complex with R-Ras

Summary for 7S0Z

• Entry DOI: 10.2210/pdb7s0z/pdb
• Descriptor: Toxin B, MAGNESIUM ION, GUANOSINE-5'-DIPHOSPHATE, ... (12 entities in total)
• Functional Keywords: toxin, substrate, enzyme, hydrolase-transferase complex, hydrolase/transferase
• Biological source: Clostridioides difficile (Peptoclostridium difficile); More
• Total number of polymer chains: 4
• Total formula weight: 169422.34

Authors

Zheng, L.,Rongsheng, J.,Peng, C. (deposition date: 2021-08-31, release date: 2021-09-08, Last modification date: 2023-10-18)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.34 Å)