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Article: Charged residues between the selectivity filter and S6 segments contribute to the permeation phenotype of the sodium channel

TitleCharged residues between the selectivity filter and S6 segments contribute to the permeation phenotype of the sodium channel
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2000
PublisherRockefeller University Press. The Journal's web site is located at www.jgp.org/
Citation
Journal Of General Physiology, 2000, v. 115 n. 1, p. 81-92 How to Cite?
AbstractThe deep regions of the Na+ channel pore around tile selectivity filter have been studied extensively; however, little is known about the adjacent linkers between the P loops and S6. The presence of conserved charged residues, including five in a row in domain III (D-III), hints that these linkers may play a role in permeation. To characterize the structural topology and function of these linkers, we neutralized the charged residues (from position 411 in D-I and its homologues in D-II, -III, and -IV to the putative start sites of S6) individually by cysteine substitution. Several cysteine mutants displayed enhanced sensitivities to Cd2+ block relative to wild-type and/or were modifiable by external sulfhydryl-specific methanethiosulfonate reagents when expressed in TSA-201 cells, indicating that these amino acids reside in the permeation pathway. While neutralization of positive charges did not alter single-channel conductance, negative charge neutralizations generally reduced conductance, suggesting that such charges facilitate ion permeation. The electrical distances for Cd2+ binding to these residues reveal a secondary 'dip' into the membrane field of the linkers in domains II and IV. Our findings demonstrate significant functional roles and surprising structural features of these previously unexplored external charged residues.
Persistent Identifierhttp://hdl.handle.net/10722/91507
ISSN
2015 Impact Factor: 4.511
2015 SCImago Journal Rankings: 3.061
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, RAen_HK
dc.contributor.authorVélez, Pen_HK
dc.contributor.authorChiamvimonvat, Nen_HK
dc.contributor.authorTomaselli, GFen_HK
dc.contributor.authorMarbán, Een_HK
dc.date.accessioned2010-09-17T10:20:31Z-
dc.date.available2010-09-17T10:20:31Z-
dc.date.issued2000en_HK
dc.identifier.citationJournal Of General Physiology, 2000, v. 115 n. 1, p. 81-92en_HK
dc.identifier.issn0022-1295en_HK
dc.identifier.urihttp://hdl.handle.net/10722/91507-
dc.description.abstractThe deep regions of the Na+ channel pore around tile selectivity filter have been studied extensively; however, little is known about the adjacent linkers between the P loops and S6. The presence of conserved charged residues, including five in a row in domain III (D-III), hints that these linkers may play a role in permeation. To characterize the structural topology and function of these linkers, we neutralized the charged residues (from position 411 in D-I and its homologues in D-II, -III, and -IV to the putative start sites of S6) individually by cysteine substitution. Several cysteine mutants displayed enhanced sensitivities to Cd2+ block relative to wild-type and/or were modifiable by external sulfhydryl-specific methanethiosulfonate reagents when expressed in TSA-201 cells, indicating that these amino acids reside in the permeation pathway. While neutralization of positive charges did not alter single-channel conductance, negative charge neutralizations generally reduced conductance, suggesting that such charges facilitate ion permeation. The electrical distances for Cd2+ binding to these residues reveal a secondary 'dip' into the membrane field of the linkers in domains II and IV. Our findings demonstrate significant functional roles and surprising structural features of these previously unexplored external charged residues.en_HK
dc.languageengen_HK
dc.publisherRockefeller University Press. The Journal's web site is located at www.jgp.org/en_HK
dc.relation.ispartofJournal of General Physiologyen_HK
dc.subjectChemicals And Cas Registry Numbersen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshEthyl Methanesulfonate - analogs & derivatives - pharmacologyen_HK
dc.subject.meshIndicators and Reagents - pharmacologyen_HK
dc.subject.meshIon Channel Gating - physiologyen_HK
dc.subject.meshMutagenesis - drug effects - physiologyen_HK
dc.subject.meshPhenotypeen_HK
dc.subject.meshSodium Channels - chemistry - drug effects - physiologyen_HK
dc.titleCharged residues between the selectivity filter and S6 segments contribute to the permeation phenotype of the sodium channelen_HK
dc.typeArticleen_HK
dc.identifier.emailLi, RA:ronaldli@hkucc.hku.hken_HK
dc.identifier.authorityLi, RA=rp01352en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1085/jgp.115.1.81en_HK
dc.identifier.pmid10613920-
dc.identifier.scopuseid_2-s2.0-0343158254en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0343158254&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume115en_HK
dc.identifier.issue1en_HK
dc.identifier.spage81en_HK
dc.identifier.epage92en_HK
dc.identifier.isiWOS:000084698500008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, RA=7404724466en_HK
dc.identifier.scopusauthoridVélez, P=6701863236en_HK
dc.identifier.scopusauthoridChiamvimonvat, N=7004461965en_HK
dc.identifier.scopusauthoridTomaselli, GF=7005223451en_HK
dc.identifier.scopusauthoridMarbán, E=8075977300en_HK

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