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dc.contributor.authorThompson, Andrewen
dc.contributor.authorAlqazzaz, Monaen
dc.contributor.authorPrice, Kerryen
dc.contributor.authorWeston, David Aen
dc.contributor.authorLummis, Sarahen
dc.date.accessioned2015-03-20T11:29:38Z
dc.date.available2015-03-20T11:29:38Z
dc.date.issued2014-09-19en
dc.identifier.citationBiochemistry, 2014, 53 (39), pp 6183–6188 DOI: 10.1021/bi5008035en
dc.identifier.issn0006-2960
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/247088
dc.description.abstractThe Erwinia ligand-gated ion channel (ELIC) is a bacterial homologue of eukaryotic Cys-loop ligand-gated ion channels. This protein has the potential to be a useful model for Cys-loop receptors but is unusual in that it has an aromatic residue (Phe) facing into the pore, leading to some predictions that this protein is incapable of ion flux. Subsequent studies have shown this is not the case, so here we probe the role of this residue by examining the function of the ELIC in cases in which the Phe has been substituted with a range of alternative amino acids, expressed in Xenopus oocytes and functionally examined. Most of the mutations have little effect on the GABA EC50, but the potency of the weak pore-blocking antagonist picrotoxinin at F16′A-, F16′D-, F16′S-, and F16′T-containing receptors was increased to levels comparable with those of Cys-loop receptors, suggesting that this antagonist can enter the pore only when residue 16′ is small. T6′S has no effect on picrotoxinin potency when expressed alone but abolishes the increased potency when combined with F16′S, indicating that the inhibitor binds at position 6′, as in Cys-loop receptors, if it can enter the pore. Overall, the data support the proposal that the ELIC pore is a good model for Cys-loop receptor pores if the role of F16′ is taken into consideration.
dc.description.sponsorshipThis project was supported by the Wellcome Trust Grant 81925 to S.C.R.L. S.C.R.L. is a Wellcome Trust Senior Research Fellow in Basic Biomedical Studies. M.A. is funded by a Yousef Jameel Scholarship. D.A.W. was funded by an MRC studentship.
dc.languageEnglishen
dc.language.isoenen
dc.publisherAmerican Chemical Society
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.titlePhenylalanine in the Pore of the Erwinia Ligand-Gated Ion Channel Modulates Picrotoxinin Potency but Not Receptor Functionen
dc.typeArticle
dc.description.versionThis is the final published version. It first appeared at http://pubs.acs.org/doi/abs/10.1021/bi5008035.en
prism.endingPage6188
prism.publicationDate2014en
prism.publicationNameBiochemistryen
prism.startingPage6183
prism.volume53en
rioxxterms.versionofrecord10.1021/bi5008035en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2014-09-19en
dc.contributor.orcidThompson, Andrew [0000-0002-7046-6792]
dc.contributor.orcidLummis, Sarah [0000-0001-9410-9805]
dc.identifier.eissn1520-4995
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (081925/Z/07/A)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales