7YVQ

Complex structure of Clostridioides difficile binary toxin folded CDTa-bound CDTb-pore (short).

This is a non-PDB format compatible entry.

Summary for 7YVQ

• Entry DOI: 10.2210/pdb7yvq/pdb
• EMDB information: 32041 32043 33188 34136
• Descriptor: ADP-ribosylating binary toxin binding subunit CdtB, ADP-ribosylating binary toxin enzymatic subunit CdtA, CALCIUM ION (3 entities in total)
• Functional Keywords: complex, translocation, oligomer, unfoldase, toxin
• Biological source: Clostridioides difficile; More
• Total number of polymer chains: 8
• Total formula weight: 579862.09

Authors

Yamada, T.,Kawamoto, A.,Yoshida, T.,Sato, Y.,Kato, T.,Tsuge, H. (deposition date: 2022-08-19, release date: 2022-10-26, Last modification date: 2024-07-03)

Primary citation

Kawamoto, A.,Yamada, T.,Yoshida, T.,Sato, Y.,Kato, T.,Tsuge, H.
Cryo-EM structures of the translocational binary toxin complex CDTa-bound CDTb-pore from Clostridioides difficile.
Nat Commun, 13:6119-6119, 2022

PubMed Abstract: Some bacteria express a binary toxin translocation system, consisting of an enzymatic subunit and translocation pore, that delivers enzymes into host cells through endocytosis. The most clinically important bacterium with such a system is Clostridioides difficile (formerly Clostridium). The CDTa and CDTb proteins from its system represent important therapeutic targets. CDTb has been proposed to be a di-heptamer, but its physiological heptameric structure has not yet been reported. Here, we report the cryo-EM structure of CDTa bound to the CDTb-pore, which reveals that CDTa binding induces partial unfolding and tilting of the first CDTa α-helix. In the CDTb-pore, an NSS-loop exists in 'in' and 'out' conformations, suggesting its involvement in substrate translocation. Finally, 3D variability analysis revealed CDTa movements from a folded to an unfolded state. These dynamic structural information provide insights into drug design against hypervirulent C. difficile strains.

PubMed: 36253419
DOI: 10.1038/s41467-022-33888-4

Experimental method

ELECTRON MICROSCOPY (3.18 Å)