6UWT

Clostridium difficile binary toxin translocase CDTb tetradecamer in symmetric conformation

Summary for 6UWT

• Entry DOI: 10.2210/pdb6uwt/pdb
• EMDB information: 20927
• Descriptor: ADP-ribosyltransferase binding component, CALCIUM ION (2 entities in total)
• Functional Keywords: cdtb, translocase, tetradecamer, toxin
• Biological source: Clostridioides difficile
• Total number of polymer chains: 14
• Total formula weight: 1046629.39

Authors

Xu, X.,Pozharski, E.,des Georges, A. (deposition date: 2019-11-05, release date: 2020-01-22, Last modification date: 2024-03-06)

Primary citation

Xu, X.,Godoy-Ruiz, R.,Adipietro, K.A.,Peralta, C.,Ben-Hail, D.,Varney, K.M.,Cook, M.E.,Roth, B.M.,Wilder, P.T.,Cleveland, T.,Grishaev, A.,Neu, H.M.,Michel, S.L.J.,Yu, W.,Beckett, D.,Rustandi, R.R.,Lancaster, C.,Loughney, J.W.,Kristopeit, A.,Christanti, S.,Olson, J.W.,MacKerell, A.D.,Georges, A.D.,Pozharski, E.,Weber, D.J.
Structure of the cell-binding component of theClostridium difficilebinary toxin reveals a di-heptamer macromolecular assembly.
Proc.Natl.Acad.Sci.USA, 117:1049-1058, 2020

PubMed Abstract: Targeting infection is challenging because treatment options are limited, and high recurrence rates are common. One reason for this is that hypervirulent strains often have a binary toxin termed the toxin, in addition to the enterotoxins TsdA and TsdB. The toxin has an enzymatic component, termed CDTa, and a pore-forming or delivery subunit termed CDTb. CDTb was characterized here using a combination of single-particle cryoelectron microscopy, X-ray crystallography, NMR, and other biophysical methods. In the absence of CDTa, 2 di-heptamer structures for activated CDTb (1.0 MDa) were solved at atomic resolution, including a symmetric (CDTb; 3.14 Å) and an asymmetric form (CDTb; 2.84 Å). Roles played by 2 receptor-binding domains of activated CDTb were of particular interest since the receptor-binding domain 1 lacks sequence homology to any other known toxin, and the receptor-binding domain 2 is completely absent in other well-studied heptameric toxins (i.e., anthrax). For CDTb, a Ca binding site was discovered in the first receptor-binding domain that is important for its stability, and the second receptor-binding domain was found to be critical for host cell toxicity and the di-heptamer fold for both forms of activated CDTb. Together, these studies represent a starting point for developing structure-based drug-design strategies to target the most severe strains of .

PubMed: 31896582
DOI: 10.1073/pnas.1919490117

Experimental method

ELECTRON MICROSCOPY (3.1 Å)