title: Binding and entry of Clostridium difficile toxin B is mediated by multiple domains.
abstract: Clostridium difficile is responsible for a number of serious gastrointestinal diseases caused primarily by two exotoxins, TcdA and TcdB. These toxins enter host cells by binding unique receptors, at least partially via their combined repetitive oligopeptides (CROPs) domains. Our study investigated structural determinants necessary for binding and entry of TcdB. Deletion analyses identified TcdB residues 1372-1493 as essential for cytotoxicity in three cell lines. Consistent with this observation, overlapping TcdB fragments (residues 1372-1848, 1372-1493 and 1493-1848) were able to independently bind cells. Our data provide new evidence supporting a more complex model of clostridial glucosylating toxin uptake than previously suggested.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO, USA.
authors.forename: Jared S
authors.initials: JS
authors.lastname: Manse
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO, USA. Electronic address: baldwinmr@missouri.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Baldwin
mesh_terms: D065567:Absorption, Physiological; D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D001692:Biological Transport; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D016360:Clostridioides difficile / Q000378:metabolism*; D003412:Cricetulus; D017353:Gene Deletion; D006801:Humans; D008958:Models, Molecular; D000075983:Nectins; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D014709:Vero Cells
chemical_list: D001427:Bacterial Toxins; D015815:Cell Adhesion Molecules; C488583:Clostridium difficile lethal toxin B; D000075983:Nectins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins
keywords: Binding; Clostridium difficile; Clostridium difficile toxin B; Combined repetitive oligopeptide; Modular binding motif (MBM); Toxicity