Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/21106
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dc.contributor.authorAlbesa-Jove, David-
dc.contributor.authorBertrand, Thomas-
dc.contributor.authorCarpenter, Elisabeth P-
dc.contributor.authorSwain, Gemma V-
dc.contributor.authorLim, Jenson-
dc.contributor.authorZhang, Jiancheng-
dc.contributor.authorHaire, Lesley F-
dc.contributor.authorVasisht, Nishi-
dc.contributor.authorBraun, Veit-
dc.contributor.authorLange, Anton-
dc.contributor.authorvon, Eichel-Streiber Christoph-
dc.contributor.authorSvergun, Dmitri I-
dc.contributor.authorFairweather, Neil F-
dc.contributor.authorBrown, Katherine A-
dc.date.accessioned2015-07-23T06:37:09Z-
dc.date.issued2010-03-12-
dc.identifier.urihttp://hdl.handle.net/1893/21106-
dc.description.abstractClostridium difficile is a nosocomial bacterial pathogen causing antibiotic-associated diarrhea and fatal pseudomembranous colitis. Key virulence factors are toxin A and toxin B (TcdB), two highly related toxins that are members of the large clostridial toxin family. These large multifunctional proteins disrupt cell function using a glucosyltransferase domain that is translocated into the cytosol after vesicular internalization of intact holotoxin. Although substantial information about the biochemical mechanisms of intoxication exists, research has been hampered by limited structural information, particularly of intact holotoxin. Here, we used small-angle X-ray scattering (SAXS) methods to obtain an ab initio low-resolution structure of native TcdB, which demonstrated that this molecule is monomeric in solution and possesses a highly asymmetric shape with a maximum dimension of approximately 275 A. Combining this SAXS information with crystallographic or modeled structures of individual functional domains of TcdB reveals for the first time that the three-dimensional structure of TcdB is organized into four distinct structural domains. Structures of the N-terminal glucosyltransferase, the cysteine protease, and the C-terminal repeat region can be aligned within three domains of the SAXS envelope. A fourth domain, predicted to be involved in the translocation of the glucosyltransferase, appears as a large solvent-exposed protrusion. Knowledge of the shapes and relative orientations of toxin domains provides new insight into defining functional domain boundaries and provides a framework for understanding how potential intra-domain interactions enable conformational changes to propagate between domains to facilitate intoxication processes.en_UK
dc.language.isoen-
dc.publisherElsevier-
dc.relationAlbesa-Jove D, Bertrand T, Carpenter EP, Swain GV, Lim J, Zhang J, Haire LF, Vasisht N, Braun V, Lange A, von Eichel-Streiber C, Svergun DI, Fairweather NF & Brown KA (2010) Four distinct structural domains in Clostridium difficile toxin B visualized using SAXS, Journal of Molecular Biology, 396 (5), pp. 1260-1270.-
dc.rightsThe publisher does not allow this work to be made publicly available in this Repository. Please use the Request a Copy feature at the foot of the Repository record to request a copy directly from the author. You can only request a copy if you wish to use this work for your own research or private study.-
dc.subjectClostridium difficileen_UK
dc.subjecttoxin Ben_UK
dc.subjectTcdBen_UK
dc.subjectSAXSen_UK
dc.subjectdomain boundariesen_UK
dc.titleFour distinct structural domains in Clostridium difficile toxin B visualized using SAXSen_UK
dc.typeJournal Articleen_UK
dc.rights.embargodate2999-12-31T00:00:00Z-
dc.rights.embargoreasonThe publisher does not allow this work to be made publicly available in this Repository therefore there is an embargo on the full text of the work.-
dc.identifier.doihttp://dx.doi.org/10.1016/j.jmb.2010.01.012-
dc.identifier.pmid20070948-
dc.citation.jtitleJournal of Molecular Biology-
dc.citation.issn0022-2836-
dc.citation.volume396-
dc.citation.issue5-
dc.citation.spage1260-
dc.citation.epage1270-
dc.citation.publicationstatusPublished-
dc.citation.peerreviewedRefereed-
dc.type.statusPublisher version (final published refereed version)-
dc.author.emailjenson.lim@stir.ac.uk-
dc.contributor.affiliationImperial College London-
dc.contributor.affiliationImperial College London-
dc.contributor.affiliationImperial College London-
dc.contributor.affiliationImperial College London-
dc.contributor.affiliationBiological and Environmental Sciences-
dc.contributor.affiliationImperial College London-
dc.contributor.affiliationMRC National Institute for Medical Research-
dc.contributor.affiliationMRC National Institute for Medical Research-
dc.contributor.affiliationtgcBIOMICS GmbH-
dc.contributor.affiliationtgcBIOMICS GmbH-
dc.contributor.affiliationJohannes Gutenberg University of Mainz-
dc.contributor.affiliationEuropean Molecular Biology Laboratory-
dc.contributor.affiliationImperial College London-
dc.contributor.affiliationImperial College London-
dc.rights.embargoterms2999-12-31-
dc.rights.embargoliftdate2999-12-31-
dc.identifier.isi000275691500006-
Appears in Collections:Biological and Environmental Sciences Journal Articles

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