{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:06:01Z","timestamp":1790165161543,"version":"4.1.0"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,3,1]]},"abstract":"<jats:p>An \u03b1-helical II\u2014III loop segment of the dihydropyridine receptor activates the ryanodine receptor calcium-release channel. We describe a novel manipulation in which this agonist's activity is increased by modifying its surface structure to resemble that of a toxin molecule. In a unique system, native \u03b2-sheet scorpion toxins have been reported to activate skeletal muscle ryanodine receptor calcium channels with high affinity by binding to the same site as the lower-affinity \u03b1-helical dihydropyridine receptor segment. We increased the alignment of basic residues in the \u03b1-helical peptide to mimic the spatial orientation of active residues in the scorpion toxin, with a consequent 2\u201420-fold increase in the activity of the \u03b1-helical peptide. We hypothesized that, like the native peptide, the modified peptide and the scorpion toxin may bind to a common site. This was supported by (i) similar changes in ryanodine receptor channel gating induced by the native or modified \u03b1-helical peptide and the \u03b2-sheet toxin, a 10\u2014100-fold reduction in channel closed time, with a \u22642-fold increase in open dwell time and (ii) a failure of the toxin to further activate channels activated by the peptides. These results suggest that diverse structural scaffolds can present similar conformational surface properties to target common receptor sites.<\/jats:p>","DOI":"10.1042\/bj20021488","type":"journal-article","created":{"date-parts":[[2003,2,24]],"date-time":"2003-02-24T15:33:03Z","timestamp":1046100783000},"page":"517-527","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The three-dimensional structural surface of two beta-sheet scorpion toxins mimics that of an alpha-helical dihydropyridine receptor segment"],"prefix":"10.1042","volume":"370","author":[{"given":"Daniel","family":"GREEN","sequence":"first","affiliation":[{"name":"Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, P.O. Box 334, Canberra, ACT, 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzi","family":"PACE","sequence":"additional","affiliation":[{"name":"Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, P.O. Box 334, Canberra, ACT, 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M.","family":"CURTIS","sequence":"additional","affiliation":[{"name":"Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, P.O. Box 334, Canberra, ACT, 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"SAKOWSKA","sequence":"additional","affiliation":[{"name":"Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, P.O. Box 334, Canberra, ACT, 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham D.","family":"LAMB","sequence":"additional","affiliation":[{"name":"Department of Zoology, La Trobe University, Kingsbury Drive, Victoria, 3086, Australia,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela F.","family":"DULHUNTY","sequence":"additional","affiliation":[{"name":"Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, P.O. Box 334, Canberra, ACT, 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco G.","family":"CASAROTTO","sequence":"additional","affiliation":[{"name":"Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, P.O. Box 334, Canberra, ACT, 2601, Australia"},{"name":"Research School of Chemistry, Australian National University, P.O. Box 334, Canberra, ACT, 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/370\/2\/517\/710555\/bj3700517.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/370\/2\/517\/710555\/bj3700517.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T12:07:46Z","timestamp":1637582866000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/370\/2\/517\/40041\/The-three-dimensional-structural-surface-of-two"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,3,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2003,3,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bj20021488","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,3,1]]}}}