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

J. Biol. Chem., Vol. 282, Issue 52, 37597-37604, December 28, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/52/37597    most recent M706437200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Neale, E. J. Articles by Sivaprasadarao, A. Search for Related Content PubMed PubMed Citation Articles by Neale, E. J. Articles by Sivaprasadarao, A. Social Bookmarking                      What's this?

Mapping the Membrane-aqueous Border for the Voltage-sensing Domain of a Potassium Channel^*

From the Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom

Voltage-sensing domains (VSDs) play diverse roles in biology. As integral components, they can detect changes in the membrane potential of a cell and couple these changes to activity of ion channels and enzymes. As independent proteins, homologues of the VSD can function as voltage-dependent proton channels. To sense voltage changes, the positively charged fourth transmembrane segment, S4, must move across the energetically unfavorable hydrophobic core of the bilayer, which presents a barrier to movement of both charged species and protons. To reduce the barrier to S4 movement, it has been suggested that aqueous crevices may penetrate the protein, reducing the extent of total movement. To investigate this hypothesis in a system containing fully functional channels in a native environment with an intact membrane potential, we have determined the contour of the membrane-aqueous border of the VSD of KvAP in Escherichia coli by examining the chemical accessibility of introduced cysteines. The results revealed the contour of the membrane-aqueous border of the VSD in its activated conformation. The water-inaccessible regions of S1 and S2 correspond to the standard width of the membrane bilayer (28 Å), but those of S3 and S4 are considerably shorter (40%), consistent with aqueous crevices pervading both the extracellular and intracellular ends. One face of S3b and the entire S3a were water-accessible, reducing the water-inaccessible region of S3 to just 10 residues, significantly shorter than for S4. The results suggest a key role for S3 in reducing the distance S4 needs to move to elicit gating.

Received for publication, August 3, 2007 , and in revised form, October 5, 2007.

^* This work was supported by Wellcome Trust Grant 076280/Z/04/Z. 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1 and 2, Movie 1, and additional references.

¹ To whom correspondence should be addressed: Inst. of Membrane and Systems Biology, Faculty of Biological Sciences, 6.44d Garstang Bldg., University of Leeds, Leeds LS2 9JT, UK. Tel.: 44-113-3434326; Fax: 44-113-343147; E-mail: a.sivaprasadarao{at}leeds.ac.uk.

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