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Structure of the full-length Clostridium difficile toxin B.
Chen, Peng; Lam, Kwok-Ho; Liu, Zheng; Mindlin, Frank A; Chen, Baohua; Gutierrez, Craig B; Huang, Lan; Zhang, Yongrong; Hamza, Therwa; Feng, Hanping; Matsui, Tsutomu; Bowen, Mark E; Perry, Kay; Jin, Rongsheng.
Afiliación
  • Chen P; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
  • Lam KH; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
  • Liu Z; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
  • Mindlin FA; Department of Physiology and Biophysics, Stony Brook University, Stony Brook, NY, USA.
  • Chen B; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
  • Gutierrez CB; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
  • Huang L; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
  • Zhang Y; Department of Microbial Pathogenesis, University of Maryland Baltimore, Baltimore, MD, USA.
  • Hamza T; Department of Microbial Pathogenesis, University of Maryland Baltimore, Baltimore, MD, USA.
  • Feng H; Department of Microbial Pathogenesis, University of Maryland Baltimore, Baltimore, MD, USA.
  • Matsui T; Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA, USA.
  • Bowen ME; Department of Physiology and Biophysics, Stony Brook University, Stony Brook, NY, USA.
  • Perry K; NE-CAT and Department of Chemistry and Chemical Biology, Cornell University, Argonne National Laboratory, Argonne, IL, USA.
  • Jin R; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA. r.jin@uci.edu.
Nat Struct Mol Biol ; 26(8): 712-719, 2019 08.
Article en En | MEDLINE | ID: mdl-31308519
ABSTRACT
Clostridium difficile is an opportunistic pathogen that establishes in the colon when the gut microbiota are disrupted by antibiotics or disease. C. difficile infection (CDI) is largely caused by two virulence factors, TcdA and TcdB. Here, we report a 3.87-Å-resolution crystal structure of TcdB holotoxin that captures a unique conformation of TcdB at endosomal pH. Complementary biophysical studies suggest that the C-terminal combined repetitive oligopeptides (CROPs) domain of TcdB is dynamic and can sample open and closed conformations that may facilitate modulation of TcdB activity in response to environmental and cellular cues during intoxication. Furthermore, we report three crystal structures of TcdB-antibody complexes that reveal how antibodies could specifically inhibit the activities of individual TcdB domains. Our studies provide novel insight into the structure and function of TcdB holotoxin and identify intrinsic vulnerabilities that could be exploited to develop new therapeutics and vaccines for the treatment of CDI.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Bacterianas / Toxinas Bacterianas / Clostridioides difficile Tipo de estudio: Prognostic_studies Idioma: En Revista: Nat Struct Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Bacterianas / Toxinas Bacterianas / Clostridioides difficile Tipo de estudio: Prognostic_studies Idioma: En Revista: Nat Struct Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos