Structural influence of hanatoxin binding on the carboxyl terminus of S3 segment in voltage-gated K+-channel Kv2.1

P. T. Huang, T. Y. Chen, L. J. Tseng, K. L. Lou, H. H. Liou, T. B. Lin, H. C. Spatz, Y. Y. Shiau

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The voltage-sensing domains of voltage-gated potassium channels Kv2.1 (drk1) contain four transmembrane segments in each subunit, termed S1 to S4. While S4 is known as the voltage sensor, the carboxyl terminus of S3 (S3C) bears a gradually broader interest concerning the site for gating modifier toxins like hanatoxin and thus the secondary structure arrangement as well as its surrounding environment. To further examine the putative three-dimensional (3-D) structure of S3C and to illustrate the residues required for hanatoxin binding (which may, in turn, show the influence on the S4 in terms of changes in channel gating), molecular simulations and dockings were performed. These were based on the solution structure of hanatoxin and the structural information from lysine-scanning results for S3C fragment. Our data suggest that several basic and acidic residues of hanatoxin are electrostatically and stereochemically mapped onto their partner residues on S3C helix, whereas some aromatic or hydrophobic residues located on the same helical fragment interact with the hydrophobic patch of the toxin upon binding. Therefore, a slight distortion of the S3C helix, in a direction toward the N-terminus of S4, may exist. Such conformational change of S3c upon toxin binding is presented as as possible explanation for the observed shift in hanatoxin binding-induced gating.

Original languageEnglish
Pages (from-to)79-85
Number of pages7
JournalReceptors and Channels
Volume8
Issue number2
DOIs
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Voltage-Gated Potassium Channels
Molecular Docking Simulation
Electric potential
Lysine
hanatoxin
Scanning
Sensors

Keywords

  • C-terminal helical structure
  • Docking and molecular simulation
  • drk1
  • Hanatoxin binding
  • Kv2.1
  • Transmembrane segment S3
  • Voltage-dependent gating

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology
  • Pharmacology

Cite this

Structural influence of hanatoxin binding on the carboxyl terminus of S3 segment in voltage-gated K+-channel Kv2.1. / Huang, P. T.; Chen, T. Y.; Tseng, L. J.; Lou, K. L.; Liou, H. H.; Lin, T. B.; Spatz, H. C.; Shiau, Y. Y.

In: Receptors and Channels, Vol. 8, No. 2, 2002, p. 79-85.

Research output: Contribution to journalArticle

Huang, P. T. ; Chen, T. Y. ; Tseng, L. J. ; Lou, K. L. ; Liou, H. H. ; Lin, T. B. ; Spatz, H. C. ; Shiau, Y. Y. / Structural influence of hanatoxin binding on the carboxyl terminus of S3 segment in voltage-gated K+-channel Kv2.1. In: Receptors and Channels. 2002 ; Vol. 8, No. 2. pp. 79-85.
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abstract = "The voltage-sensing domains of voltage-gated potassium channels Kv2.1 (drk1) contain four transmembrane segments in each subunit, termed S1 to S4. While S4 is known as the voltage sensor, the carboxyl terminus of S3 (S3C) bears a gradually broader interest concerning the site for gating modifier toxins like hanatoxin and thus the secondary structure arrangement as well as its surrounding environment. To further examine the putative three-dimensional (3-D) structure of S3C and to illustrate the residues required for hanatoxin binding (which may, in turn, show the influence on the S4 in terms of changes in channel gating), molecular simulations and dockings were performed. These were based on the solution structure of hanatoxin and the structural information from lysine-scanning results for S3C fragment. Our data suggest that several basic and acidic residues of hanatoxin are electrostatically and stereochemically mapped onto their partner residues on S3C helix, whereas some aromatic or hydrophobic residues located on the same helical fragment interact with the hydrophobic patch of the toxin upon binding. Therefore, a slight distortion of the S3C helix, in a direction toward the N-terminus of S4, may exist. Such conformational change of S3c upon toxin binding is presented as as possible explanation for the observed shift in hanatoxin binding-induced gating.",
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AU - Lou, K. L.

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AU - Spatz, H. C.

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AB - The voltage-sensing domains of voltage-gated potassium channels Kv2.1 (drk1) contain four transmembrane segments in each subunit, termed S1 to S4. While S4 is known as the voltage sensor, the carboxyl terminus of S3 (S3C) bears a gradually broader interest concerning the site for gating modifier toxins like hanatoxin and thus the secondary structure arrangement as well as its surrounding environment. To further examine the putative three-dimensional (3-D) structure of S3C and to illustrate the residues required for hanatoxin binding (which may, in turn, show the influence on the S4 in terms of changes in channel gating), molecular simulations and dockings were performed. These were based on the solution structure of hanatoxin and the structural information from lysine-scanning results for S3C fragment. Our data suggest that several basic and acidic residues of hanatoxin are electrostatically and stereochemically mapped onto their partner residues on S3C helix, whereas some aromatic or hydrophobic residues located on the same helical fragment interact with the hydrophobic patch of the toxin upon binding. Therefore, a slight distortion of the S3C helix, in a direction toward the N-terminus of S4, may exist. Such conformational change of S3c upon toxin binding is presented as as possible explanation for the observed shift in hanatoxin binding-induced gating.

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