The signature sequence of voltage-gated potassium channels projects into the external vestibule.

The Journal of Biological Chemistry
J AiyarK G Chandy

Abstract

A highly conserved motif, GYGD, contributes to the formation of the ion selectivity filter in voltage-gated K+ channels and is thought to interact with the scorpion toxin residue, Lys27. By probing the pore of the Kv1.3 channel with synthetic kaliotoxin-Lys27 mutants, each containing a non-natural lysine analog of a different length, and using mutant cycle analysis, we determined the spatial locations of Tyr400 and Asp402 in the GYGD motif, relative to His404 located at the base of the outer vestibule. Our data indicate that the terminal amines of the shorter Lys27 analogs lie close to His404 and to Asp402, while Lys27 itself interacts with Tyr400. Based on these data, we developed a molecular model of this region of the channel. The junction between the outer vestibule and the pore is defined by a ring ( approximately 8-9-A diameter) formed from alternating Asp402 and His404 residues. Tyr400 lies 4-6 A deeper into the pore, and its interaction with kaliotoxin-Lys27 is in competition with K+ ions. Studies with dimeric Kv1.3 constructs suggest that two Tyr400 residues in the tetramer are sufficient to bind K+ ions. Thus, at least part of the K+ channel signature sequence extends into a shallow trough at the center of a wide exte...Continue Reading

References

Jan 1, 1992·Methods in Enzymology·H Soreq, S Seidman
Jan 1, 1992·Annual Review of Physiology·L Y Jan, Y N Jan
Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S GrissmerK G Chandy
Mar 1, 1988·The Journal of General Physiology·R MacKinnon, C Miller
Oct 1, 1993·Biophysical Journal·S A Goldstein, C Miller
Jan 20, 1995·Science·T Clackson, J A Wells
Jan 1, 1995·Annual Review of Immunology·R S Lewis, M D Cahalan
Apr 1, 1994·Biophysical Journal·L HeginbothamR MacKinnon
Feb 1, 1996·Neuron·A Gross, R MacKinnon

❮ Previous
Next ❯

Citations

Jun 1, 2001·Toxicon : Official Journal of the International Society on Toxinology·K G ChandyG A Gutman
Aug 9, 2003·Toxicon : Official Journal of the International Society on Toxinology·Ming-Hua LiGuo-Yuan Hu
Jul 9, 1998·Toxicon : Official Journal of the International Society on Toxinology·T Olamendi-PortugalL D Possani
Oct 29, 1998·Toxicon : Official Journal of the International Society on Toxinology·M L GarciaG J Kaczorowski
May 28, 2003·Trends in Pharmacological Sciences·Ricardo C Rodríguez de la VegaLourival D Possani
Jan 16, 1998·Cellular Signalling·N Dascal
Jan 13, 1998·Current Opinion in Biotechnology·M D Cahalan, K G Chandy
Sep 26, 2014·Expert Opinion on Drug Metabolism & Toxicology·János TajtiLászló Vécsei
Sep 16, 2014·Expert Opinion on Investigational Drugs·László VécseiJános Tajti
May 21, 2010·Expert Opinion on Investigational Drugs·Michael J M Fischer
Jan 8, 2016·Critical Reviews in Biochemistry and Molecular Biology·Klara R KleinKathleen M Caron
Sep 25, 2015·Clinical and Experimental Immunology·S TakanoM Takaso
Jan 14, 2012·Toxicon : Official Journal of the International Society on Toxinology·Limei ZhuShunyi Zhu
Nov 10, 2015·The Journal of Physical Chemistry. B·Eva MeirovitchJordan H Chill
Sep 17, 2009·Immunological Reviews·Michael D Cahalan, K George Chandy
Jun 23, 2004·Toxicon : Official Journal of the International Society on Toxinology·Kathleen M GiangiacomoTheodore J Mullmann
Jun 23, 2004·Toxicon : Official Journal of the International Society on Toxinology·Sylvaine GaspariniAndré Ménez
Jun 23, 2004·Toxicon : Official Journal of the International Society on Toxinology·Violeta VisanStephan Grissmer
Mar 21, 2007·Biophysical Journal·Adam P HillJ I Vandenberg
Dec 3, 2014·Cell Calcium·Luigi LeanzaKatrin Anne Becker
Sep 19, 2016·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·O V NekrasovaA V Feofanov
Sep 24, 1998·Trends in Pharmacological Sciences·J M Hall, D M Smith
Sep 15, 1998·Journal of Molecular Biology·H L LiB K Jap
Jun 23, 2009·Expert Opinion on Therapeutic Targets·Srikant RangarajuK George Chandy
Jul 9, 2004·American Journal of Physiology. Cell Physiology·Matthew D FullerNael A McCarty
May 23, 2002·FEBS Letters·Kenji KuwasakoTanenao Eto
Mar 13, 2003·Journal of Peptide Science : an Official Publication of the European Peptide Society·A M C PimentaM F Martin-Eauclaire

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.