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dc.contributor.authorBoesze-Battaglia, Kathleen
dc.contributor.authorWalker, Lisa P.
dc.contributor.authorZekavat, Ali
dc.contributor.authorDlakic, Mensur
dc.contributor.authorScuron, Monika Damek
dc.contributor.authorNygrend, Patrik
dc.contributor.authorShenker, Bruce J.
dc.date.accessioned2015-12-28T19:50:04Z
dc.date.available2015-12-28T19:50:04Z
dc.date.issued2015-07
dc.identifier.citationBoesze-Battaglia, Kathleen, Lisa P. Walker, Ali Zekavat, Mensur Dlakic, Monika Damek Scuron, Patrik Nygrend, and Bruce J. Shenker. "The Aggregatibacter actinomycetemcomitans cytolethal distending toxin active subunit, CdtB, contains a cholesterol recognition sequence required for toxin binding and subunit internalization." Infection & Immunity (July 2015). DOI:https://dx.doi.org/10.1128/IAI.00788-15.en_US
dc.identifier.issn0019-9567
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/9463
dc.description.abstractInduction of cell cycle arrest in lymphocytes following exposure to the Aggregatibacter actinomycetemcomitans cytolethal distending toxin (Cdt) is dependent upon the integrity of lipid membrane microdomains. Moreover, we have previously demonstrated that the associaton of Cdt with target cells involves the CdtC subunit which binds to cholesterol via a cholesterol recognition amino acid consensus sequence (CRAC site). In this study we demonstrate that the active Cdt subunit, CdtB, also is capable of binding to large unilamellar vesicles (LUVs) containing cholesterol. Furthermore, CdtB binding to cholesterol involves a similar CRAC site as that demonstrated for CdtC. Mutation of the CRAC site reduces binding to model membranes as well as toxin binding and CdtB internalization in both Jurkat cells and human macrophages. A concomitant reduction in Cdt-induced toxicity was also noted indicated by reduced cell cycle arrest and apoptosis in Jurkat cells and a reduction in the pro-inflammatory response in macrophages (IL-1β and TNFα release). Collectively, these observations indicate that membrane cholesterol serves as an essential ligand for both CdtC and CdtB and further, that this binding is necessary for both internalization of CdtB and subsequent molecular events leading to intoxication of cells.en_US
dc.description.sponsorshipNational Institutes of Health grants DE06014 and DE023071.en_US
dc.titleThe Aggregatibacter actinomycetemcomitans cytolethal distending toxin active subunit, CdtB, contains a cholesterol recognition sequence required for toxin binding and subunit internalizationen_US
dc.typeArticleen_US
mus.citation.extentfirstpage4042en_US
mus.citation.extentlastpage4055en_US
mus.citation.issue10en_US
mus.citation.journaltitleInfection & Immunityen_US
mus.citation.volume83en_US
mus.identifier.categoryLife Sciences & Earth Sciencesen_US
mus.identifier.doi10.1128/IAI.00788-15en_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.contributor.orcidDlakic, Mensur|0000-0003-4315-1514en_US


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