Linked Life Data

15054090

Source:http://linkedlifedata.com/resource/pubmed/id/15054090

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-3-31
pubmed:abstractText
Gating modifiers constitute a large group of polypeptide toxins that interact with the voltage-sensing module of ion channels. Among them, scorpion beta-toxins induce a negative shift in the voltage dependence of sodium channel activation. To explain their effect, a "voltage sensor trapping" model has been proposed in which the voltage sensor of domain-II (DIIS4) is trapped in an outward, activated position by a prebound beta-toxin upon membrane depolarization. Whereas toxin effect on channel activation was enhanced upon neutralization of the two outermost arginines in DIIS4, toxin residues involved in sensor trapping have not been identified. Using the scorpion excitatory beta-toxin, Bj-xtrIT, we found two conserved acidic residues, Glu15 and Glu30, mandatory for toxin action. Whereas mutagenesis of Glu30 affected both toxicity and binding affinity, substitutions E15A/F abolished activity but had minor effects on binding. Complete uncoupling of activity from binding was obtained with mutant E15R, acting as an efficient antagonist of Bj-xtrIT. On the basis of the voltage sensor trapping model and our results, we propose that Glu15 interacts with the emerging gating charges of DIIS4 upon membrane depolarization. Conserved acidic residues found in a variety of gating modifiers from scorpions and spiders may interact similarly with the voltage sensor.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
683-9
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Conversion of a scorpion toxin agonist into an antagonist highlights an acidic residue involved in voltage sensor trapping during activation of neuronal Na+ channels.
pubmed:affiliation
Department of Plant Sciences, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.
pubmed:publicationType
Journal Article