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dc.contributor.authorAlbesa-Jove, Daviden_UK
dc.contributor.authorBertrand, Thomasen_UK
dc.contributor.authorCarpenter, Elisabeth Pen_UK
dc.contributor.authorSwain, Gemma Ven_UK
dc.contributor.authorLim, Jensonen_UK
dc.contributor.authorZhang, Jianchengen_UK
dc.contributor.authorHaire, Lesley Fen_UK
dc.contributor.authorVasisht, Nishien_UK
dc.contributor.authorBraun, Veiten_UK
dc.contributor.authorLange, Antonen_UK
dc.contributor.authorvon Eichel-Streiber, Christophen_UK
dc.contributor.authorSvergun, Dmitri Ien_UK
dc.contributor.authorFairweather, Neil Fen_UK
dc.contributor.authorBrown, Katherine Aen_UK
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.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.en_UK
dc.subjectClostridium difficileen_UK
dc.subjecttoxin Ben_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.embargoreason[JMB 2012.pdf] The 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.en_UK
dc.citation.jtitleJournal of Molecular Biologyen_UK
dc.type.statusVoR - Version of Recorden_UK
dc.contributor.affiliationImperial College Londonen_UK
dc.contributor.affiliationImperial College Londonen_UK
dc.contributor.affiliationImperial College Londonen_UK
dc.contributor.affiliationImperial College Londonen_UK
dc.contributor.affiliationBiological and Environmental Sciencesen_UK
dc.contributor.affiliationImperial College Londonen_UK
dc.contributor.affiliationMRC National Institute for Medical Researchen_UK
dc.contributor.affiliationMRC National Institute for Medical Researchen_UK
dc.contributor.affiliationtgcBIOMICS GmbHen_UK
dc.contributor.affiliationtgcBIOMICS GmbHen_UK
dc.contributor.affiliationJohannes Gutenberg University of Mainzen_UK
dc.contributor.affiliationEuropean Molecular Biology Laboratoryen_UK
dc.contributor.affiliationImperial College Londonen_UK
dc.contributor.affiliationImperial College Londonen_UK
rioxxterms.typeJournal Article/Reviewen_UK
local.rioxx.authorAlbesa-Jove, David|en_UK
local.rioxx.authorBertrand, Thomas|en_UK
local.rioxx.authorCarpenter, Elisabeth P|en_UK
local.rioxx.authorSwain, Gemma V|en_UK
local.rioxx.authorLim, Jenson|0000-0001-7417-356Xen_UK
local.rioxx.authorZhang, Jiancheng|en_UK
local.rioxx.authorHaire, Lesley F|en_UK
local.rioxx.authorVasisht, Nishi|en_UK
local.rioxx.authorBraun, Veit|en_UK
local.rioxx.authorLange, Anton|en_UK
local.rioxx.authorvon Eichel-Streiber, Christoph|en_UK
local.rioxx.authorSvergun, Dmitri I|en_UK
local.rioxx.authorFairweather, Neil F|en_UK
local.rioxx.authorBrown, Katherine A|en_UK
local.rioxx.projectInternal Project|University of Stirling|
local.rioxx.filenameJMB 2012.pdfen_UK
Appears in Collections:Biological and Environmental Sciences Journal Articles

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