HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 1, 572-581, January 4, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/1/572    most recent M706811200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Paukert, M. Articles by Gründer, S. Search for Related Content PubMed PubMed Citation Articles by Paukert, M. Articles by Gründer, S. Social Bookmarking                      What's this?

Candidate Amino Acids Involved in H⁺ Gating of Acid-sensing Ion Channel 1a^*

Martin Paukert¹, Xuanmao Chen, Georg Polleichtner, Hermann Schindelin^¶, and Stefan Gründer²

From the Department of Physiology II, University of Tübingen, Gmelinstrasse 5, 72076 Tübingen, the Department of Physiology II, University of Würzburg, Röntgenring 9, 97070 Würzburg, and the ^¶Rudolf Virchow Center for Experimental Biomedicine and Institute of Structural Biology, University of Würzburg, Versbacher Strasse 9, 97078 Würzburg, Germany

Acid-sensing ion channels are ligand-gated cation channels, gated by extracellular H⁺. H⁺ is the simplest ligand possible, and whereas for larger ligands that gate ion channels complex binding sites in the three-dimensional structure of the proteins have to be assumed, H⁺ could in principle gate a channel by titration of a single amino acid. Experimental evidence suggests a more complex situation, however. For example, it has been shown that extracellular Ca²⁺ ions compete with H⁺; probably Ca²⁺ ions bound to the extracellular loop of ASICs stabilize the closed state of the channel and have to be displaced before the channel can open. In such a scheme, amino acids contributing to Ca²⁺ binding would also be candidates contributing to H⁺ gating. In this study we systematically screened more than 40 conserved, charged amino acids in the extracellular region of ASIC1a for a possible contribution to H⁺ gating. We identified four amino acids where substitution strongly affects H⁺ gating: Glu⁶³, His⁷²/His⁷³, and Asp⁷⁸. These amino acids are highly conserved among H⁺-sensitive ASICs and are candidates for the "H⁺ sensor" of ASICs.

Received for publication, August 15, 2007 , and in revised form, October 31, 2007.

^* This work was supported by Deutsche Forschungsgemeinschaft Grants GR1771/3-3 and GR1771/3-4 (to S. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence may be addressed: Solomon H. Snyder Dept. of Neuroscience, Johns Hopkins University, 725 N. Wolfe St., WBSB 1001, Baltimore, MD 21205. Tel.: 410-955-6949; Fax: 410-955-6942; E-mail: mpauker1{at}jhmi.edu.

² To whom correspondence may be addressed: Dept. of Physiology II, Röntgenring 9, D-97070 Würzburg, Germany. Tel.: 49-931-31-6046; Fax: 49-931-31-2741; E-mail: stefan.gruender{at}uni-wuerzburg.de.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. Li, Y. Yang, and C. M. Canessa Interaction of the Aromatics Tyr-72/Trp-288 in the Interface of the Extracellular and Transmembrane Domains Is Essential for Proton Gating of Acid-sensing Ion Channels J. Biol. Chem., February 13, 2009; 284(7): 4689 - 4694. [Abstract] [Full Text] [PDF]

				M. K. Schnizler, K. Schnizler, X.-m. Zha, D. D. Hall, J. A. Wemmie, J. W. Hell, and M. J. Welsh The Cytoskeletal Protein {alpha}-Actinin Regulates Acid-sensing Ion Channel 1a through a C-terminal Interaction J. Biol. Chem., January 30, 2009; 284(5): 2697 - 2705. [Abstract] [Full Text] [PDF]

				D. M. Collier and P. M. Snyder Extracellular Protons Regulate Human ENaC by Modulating Na+ Self-inhibition J. Biol. Chem., January 9, 2009; 284(2): 792 - 798. [Abstract] [Full Text] [PDF]