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The Aggregatibacter...
The Aggregatibacter actinomycetemcomitans Cytolethal Distending Toxin Active Subunit CdtB Contains a Cholesterol Recognition Sequence Required for Toxin Binding and Subunit Internalization
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- Boesze-Battaglia, Kathleen (författare)
- University of Penn, PA 19104 USA
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- Walker, Lisa P. (författare)
- University of Penn, PA 19104 USA
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- Zekavat, Ali (författare)
- University of Penn, PA 19104 USA
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- Dlakic, Mensur (författare)
- Montana State University, MT 59717 USA
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- Damek Scuron, Monika (författare)
- University of Penn, PA 19104 USA
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- Nygren, Patrik (författare)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Shenker, Bruce J. (författare)
- University of Penn, PA 19104 USA
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(creator_code:org_t)
- AMER SOC MICROBIOLOGY, 2015
- 2015
- Engelska.
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Ingår i: Infection and Immunity. - : AMER SOC MICROBIOLOGY. - 0019-9567 .- 1098-5522. ; 83:10, s. 4042-4055
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Induction 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 association 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 proinflammatory response in macrophages (interleukin 1 beta [IL-1 beta] and tumor necrosis factor alpha [TNF-alpha] 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.
Ämnesord
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
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