View in EDS PDF Full Text

Botulinum Neurotoxin Is Shielded by NTNHA in an Interlocked Complex.

Saved in:
Bibliographic Details
Title: Botulinum Neurotoxin Is Shielded by NTNHA in an Interlocked Complex.
Authors: Gu, Shenyan, Rumpel, Sophie, Jie Zhou, Strotmeier, Jasmin, Bigalke, Hans, Perry, Kay, Shoemaker, Charles B., Rummel, Andreas, Rongsheng Jin
Source: Science (pre-March 2025). 2/24/2012, Vol. 335 Issue 6071, p977-981. 5p.
Subjects: Crystal structure research, Botulinum toxin, Hemagglutinin, Clostridium botulinum, Food contamination, Molecular microbiology
Abstract: Botulinum neurotoxins (BoNTs) are highly poisonous substances that are also effective medicines. Accidental BoNT poisoning often occurs through ingestion of Clostridium botulinum—contaminated food. Here, we present the crystal structure of a BoNT in complex with a clostridial nontoxic nonhemagglutinin (NTNHA) protein at 2.7 angstroms. Biochemical and functional studies show that NTNHA provides large and multivalent binding interfaces to protect BoNT from gastrointestinal degradation. Moreover, the structure highlights key residues in BoNT that regulate complex assembly in a pH-dependent manner. Collectively, our findings define the molecular mechanisms by which NTNHA shields BoNT in the hostile gastrointestinal environment and releases it upon entry into the circulation. These results will assist in the design of small molecules for inhibiting oral BoNT intoxication and of delivery vehicles for oral administration of biologics. [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
Header DbId: pbh
DbLabel: Psychology and Behavioral Sciences Collection
An: 74261984
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Botulinum Neurotoxin Is Shielded by NTNHA in an Interlocked Complex.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Gu%2C+Shenyan%22">Gu, Shenyan</searchLink><br /><searchLink fieldCode="AR" term="%22Rumpel%2C+Sophie%22">Rumpel, Sophie</searchLink><br /><searchLink fieldCode="AR" term="%22Jie+Zhou%22">Jie Zhou</searchLink><br /><searchLink fieldCode="AR" term="%22Strotmeier%2C+Jasmin%22">Strotmeier, Jasmin</searchLink><br /><searchLink fieldCode="AR" term="%22Bigalke%2C+Hans%22">Bigalke, Hans</searchLink><br /><searchLink fieldCode="AR" term="%22Perry%2C+Kay%22">Perry, Kay</searchLink><br /><searchLink fieldCode="AR" term="%22Shoemaker%2C+Charles+B%2E%22">Shoemaker, Charles B.</searchLink><br /><searchLink fieldCode="AR" term="%22Rummel%2C+Andreas%22">Rummel, Andreas</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>. 2/24/2012, Vol. 335 Issue 6071, p977-981. 5p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Crystal+structure+research%22">Crystal structure research</searchLink><br /><searchLink fieldCode="DE" term="%22Botulinum+toxin%22">Botulinum toxin</searchLink><br /><searchLink fieldCode="DE" term="%22Hemagglutinin%22">Hemagglutinin</searchLink><br /><searchLink fieldCode="DE" term="%22Clostridium+botulinum%22">Clostridium botulinum</searchLink><br /><searchLink fieldCode="DE" term="%22Food+contamination%22">Food contamination</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+microbiology%22">Molecular microbiology</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Botulinum neurotoxins (BoNTs) are highly poisonous substances that are also effective medicines. Accidental BoNT poisoning often occurs through ingestion of Clostridium botulinum—contaminated food. Here, we present the crystal structure of a BoNT in complex with a clostridial nontoxic nonhemagglutinin (NTNHA) protein at 2.7 angstroms. Biochemical and functional studies show that NTNHA provides large and multivalent binding interfaces to protect BoNT from gastrointestinal degradation. Moreover, the structure highlights key residues in BoNT that regulate complex assembly in a pH-dependent manner. Collectively, our findings define the molecular mechanisms by which NTNHA shields BoNT in the hostile gastrointestinal environment and releases it upon entry into the circulation. These results will assist in the design of small molecules for inhibiting oral BoNT intoxication and of delivery vehicles for oral administration of biologics. [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.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=74261984
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1126/science.1214270
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 5
        StartPage: 977
    Subjects:
      – SubjectFull: Crystal structure research
        Type: general
      – SubjectFull: Botulinum toxin
        Type: general
      – SubjectFull: Hemagglutinin
        Type: general
      – SubjectFull: Clostridium botulinum
        Type: general
      – SubjectFull: Food contamination
        Type: general
      – SubjectFull: Molecular microbiology
        Type: general
    Titles:
      – TitleFull: Botulinum Neurotoxin Is Shielded by NTNHA in an Interlocked Complex.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Gu, Shenyan
      – PersonEntity:
          Name:
            NameFull: Rumpel, Sophie
      – PersonEntity:
          Name:
            NameFull: Jie Zhou
      – PersonEntity:
          Name:
            NameFull: Strotmeier, Jasmin
      – PersonEntity:
          Name:
            NameFull: Bigalke, Hans
      – PersonEntity:
          Name:
            NameFull: Perry, Kay
      – PersonEntity:
          Name:
            NameFull: Shoemaker, Charles B.
      – PersonEntity:
          Name:
            NameFull: Rummel, Andreas
      – PersonEntity:
          Name:
            NameFull: Rongsheng Jin
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 24
              M: 02
              Text: 2/24/2012
              Type: published
              Y: 2012
          Identifiers:
            – Type: issn-print
              Value: 00368075
          Numbering:
            – Type: volume
              Value: 335
            – Type: issue
              Value: 6071
          Titles:
            – TitleFull: Science (pre-March 2025)
              Type: main
ResultId 1