Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex.
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| Title: | Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex. |
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| Authors: | Kwangkook Lee, Xiaofen Zhong, Shenyan Gu, Kruel, Anna Magdalena, Dorner, Martin B., Perry, Kay, Rummel, Andreas, Min Dong, Rongsheng Jin |
| Source: | Science (pre-March 2025). 6/20/2014, Vol. 344 Issue 6190, p1405-1410. 6p. |
| Subjects: | Botulinum toxin, Hemagglutinin -- Structure, Serotypes, Cadherins, Molecular cell adhesion, Botulism, Molecular structure of complex compounds |
| Abstract: | How botulinum neurotoxins (BoNTs) cross the host intestinal epithelial barrier in foodborne botulism is poorly understood. Here, we present the crystal structure of a clostridial hemagglutinin (HA) complex of serotype BoNT/A bound to the cell adhesion protein E-cadherin at 2.4 angstroms. The HA complex recognizes E-cadherin with high specificity involving extensive intermolecular interactions and also binds to carbohydrates on the cell surface. Binding of the HA complex sequesters E-cadherin in the monomeric state, compromising the E-cadherin-mediated intercellular barrier and facilitating paracellular absorption of BoNT/A. We reconstituted the complete 14-subunit BoNT/A complex using recombinantly produced components and demonstrated that abolishing either E-cadherin- or carbohydrate-binding of the HA complex drastically reduces oral toxicity of BoNT/A complex in vivo. Together, these studies establish the molecular mechanism of how HAs contribute to the oral toxicity of BoNT/A. [ABSTRACT FROM AUTHOR] |
| Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 96878499 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Kwangkook+Lee%22">Kwangkook Lee</searchLink><br /><searchLink fieldCode="AR" term="%22Xiaofen+Zhong%22">Xiaofen Zhong</searchLink><br /><searchLink fieldCode="AR" term="%22Shenyan+Gu%22">Shenyan Gu</searchLink><br /><searchLink fieldCode="AR" term="%22Kruel%2C+Anna+Magdalena%22">Kruel, Anna Magdalena</searchLink><br /><searchLink fieldCode="AR" term="%22Dorner%2C+Martin+B%2E%22">Dorner, Martin B.</searchLink><br /><searchLink fieldCode="AR" term="%22Perry%2C+Kay%22">Perry, Kay</searchLink><br /><searchLink fieldCode="AR" term="%22Rummel%2C+Andreas%22">Rummel, Andreas</searchLink><br /><searchLink fieldCode="AR" term="%22Min+Dong%22">Min Dong</searchLink><br /><searchLink fieldCode="AR" term="%22Rongsheng+Jin%22">Rongsheng Jin</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 6/20/2014, Vol. 344 Issue 6190, p1405-1410. 6p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Botulinum+toxin%22">Botulinum toxin</searchLink><br /><searchLink fieldCode="DE" term="%22Hemagglutinin+--+Structure%22">Hemagglutinin -- Structure</searchLink><br /><searchLink fieldCode="DE" term="%22Serotypes%22">Serotypes</searchLink><br /><searchLink fieldCode="DE" term="%22Cadherins%22">Cadherins</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+cell+adhesion%22">Molecular cell adhesion</searchLink><br /><searchLink fieldCode="DE" term="%22Botulism%22">Botulism</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+structure+of+complex+compounds%22">Molecular structure of complex compounds</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: How botulinum neurotoxins (BoNTs) cross the host intestinal epithelial barrier in foodborne botulism is poorly understood. Here, we present the crystal structure of a clostridial hemagglutinin (HA) complex of serotype BoNT/A bound to the cell adhesion protein E-cadherin at 2.4 angstroms. The HA complex recognizes E-cadherin with high specificity involving extensive intermolecular interactions and also binds to carbohydrates on the cell surface. Binding of the HA complex sequesters E-cadherin in the monomeric state, compromising the E-cadherin-mediated intercellular barrier and facilitating paracellular absorption of BoNT/A. We reconstituted the complete 14-subunit BoNT/A complex using recombinantly produced components and demonstrated that abolishing either E-cadherin- or carbohydrate-binding of the HA complex drastically reduces oral toxicity of BoNT/A complex in vivo. Together, these studies establish the molecular mechanism of how HAs contribute to the oral toxicity of BoNT/A. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1126/science.1253823 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 6 StartPage: 1405 Subjects: – SubjectFull: Botulinum toxin Type: general – SubjectFull: Hemagglutinin -- Structure Type: general – SubjectFull: Serotypes Type: general – SubjectFull: Cadherins Type: general – SubjectFull: Molecular cell adhesion Type: general – SubjectFull: Botulism Type: general – SubjectFull: Molecular structure of complex compounds Type: general Titles: – TitleFull: Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Kwangkook Lee – PersonEntity: Name: NameFull: Xiaofen Zhong – PersonEntity: Name: NameFull: Shenyan Gu – PersonEntity: Name: NameFull: Kruel, Anna Magdalena – PersonEntity: Name: NameFull: Dorner, Martin B. – PersonEntity: Name: NameFull: Perry, Kay – PersonEntity: Name: NameFull: Rummel, Andreas – PersonEntity: Name: NameFull: Min Dong – PersonEntity: Name: NameFull: Rongsheng Jin IsPartOfRelationships: – BibEntity: Dates: – D: 20 M: 06 Text: 6/20/2014 Type: published Y: 2014 Identifiers: – Type: issn-print Value: 00368075 Numbering: – Type: volume Value: 344 – Type: issue Value: 6190 Titles: – TitleFull: Science (pre-March 2025) Type: main |
| ResultId | 1 |
