Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR.
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| Title: | Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR. |
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| Authors: | Lange, Adam, Giller, Karin, Hornig, Sönke, Martin-Eauclaire, Marie-France, Pongs, Olaf, Becker, Stefan, Baldus, Marc |
| Source: | Nature. 4/13/2006, Vol. 440 Issue 7086, p959-962. 4p. 4 Charts. |
| Subjects: | Toxins, Potassium channels, Scorpion venom, Membrane proteins, Binding sites, Nuclear magnetic resonance |
| Abstract: | The active site of potassium (K+) channels catalyses the transport of K+ ions across the plasma membrane—similar to the catalytic function of the active site of an enzyme—and is inhibited by toxins from scorpion venom. On the basis of the conserved structures of K+ pore regions and scorpion toxins, detailed structures for the K+ channel–scorpion toxin binding interface have been proposed. In these models and in previous solution-state nuclear magnetic resonance (NMR) studies using detergent-solubilized membrane proteins, scorpion toxins were docked to the extracellular entrance of the K+ channel pore assuming rigid, preformed binding sites. Using high-resolution solid-state NMR spectroscopy, here we show that high-affinity binding of the scorpion toxin kaliotoxin to a chimaeric K+ channel (KcsA-Kv1.3) is associated with significant structural rearrangements in both molecules. Our approach involves a combined analysis of chemical shifts and proton–proton distances and demonstrates that solid-state NMR is a sensitive method for analysing the structure of a membrane protein–inhibitor complex. We propose that structural flexibility of the K+ channel and the toxin represents an important determinant for the high specificity of toxin–K+ channel interactions. [ABSTRACT FROM AUTHOR] |
| Copyright of Nature is the property of Springer Nature 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: 20468520 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Lange%2C+Adam%22">Lange, Adam</searchLink><br /><searchLink fieldCode="AR" term="%22Giller%2C+Karin%22">Giller, Karin</searchLink><br /><searchLink fieldCode="AR" term="%22Hornig%2C+Sönke%22">Hornig, Sönke</searchLink><br /><searchLink fieldCode="AR" term="%22Martin-Eauclaire%2C+Marie-France%22">Martin-Eauclaire, Marie-France</searchLink><br /><searchLink fieldCode="AR" term="%22Pongs%2C+Olaf%22">Pongs, Olaf</searchLink><br /><searchLink fieldCode="AR" term="%22Becker%2C+Stefan%22">Becker, Stefan</searchLink><br /><searchLink fieldCode="AR" term="%22Baldus%2C+Marc%22">Baldus, Marc</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Nature%22">Nature</searchLink>. 4/13/2006, Vol. 440 Issue 7086, p959-962. 4p. 4 Charts. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Toxins%22">Toxins</searchLink><br /><searchLink fieldCode="DE" term="%22Potassium+channels%22">Potassium channels</searchLink><br /><searchLink fieldCode="DE" term="%22Scorpion+venom%22">Scorpion venom</searchLink><br /><searchLink fieldCode="DE" term="%22Membrane+proteins%22">Membrane proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Binding+sites%22">Binding sites</searchLink><br /><searchLink fieldCode="DE" term="%22Nuclear+magnetic+resonance%22">Nuclear magnetic resonance</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: The active site of potassium (K+) channels catalyses the transport of K+ ions across the plasma membrane—similar to the catalytic function of the active site of an enzyme—and is inhibited by toxins from scorpion venom. On the basis of the conserved structures of K+ pore regions and scorpion toxins, detailed structures for the K+ channel–scorpion toxin binding interface have been proposed. In these models and in previous solution-state nuclear magnetic resonance (NMR) studies using detergent-solubilized membrane proteins, scorpion toxins were docked to the extracellular entrance of the K+ channel pore assuming rigid, preformed binding sites. Using high-resolution solid-state NMR spectroscopy, here we show that high-affinity binding of the scorpion toxin kaliotoxin to a chimaeric K+ channel (KcsA-Kv1.3) is associated with significant structural rearrangements in both molecules. Our approach involves a combined analysis of chemical shifts and proton–proton distances and demonstrates that solid-state NMR is a sensitive method for analysing the structure of a membrane protein–inhibitor complex. We propose that structural flexibility of the K+ channel and the toxin represents an important determinant for the high specificity of toxin–K+ channel interactions. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Nature is the property of Springer Nature 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: 10.1038/nature04649 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 4 StartPage: 959 Subjects: – SubjectFull: Toxins Type: general – SubjectFull: Potassium channels Type: general – SubjectFull: Scorpion venom Type: general – SubjectFull: Membrane proteins Type: general – SubjectFull: Binding sites Type: general – SubjectFull: Nuclear magnetic resonance Type: general Titles: – TitleFull: Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Lange, Adam – PersonEntity: Name: NameFull: Giller, Karin – PersonEntity: Name: NameFull: Hornig, Sönke – PersonEntity: Name: NameFull: Martin-Eauclaire, Marie-France – PersonEntity: Name: NameFull: Pongs, Olaf – PersonEntity: Name: NameFull: Becker, Stefan – PersonEntity: Name: NameFull: Baldus, Marc IsPartOfRelationships: – BibEntity: Dates: – D: 13 M: 04 Text: 4/13/2006 Type: published Y: 2006 Identifiers: – Type: issn-print Value: 00280836 Numbering: – Type: volume Value: 440 – Type: issue Value: 7086 Titles: – TitleFull: Nature Type: main |
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