{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:36:28Z","timestamp":1790498188998,"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":[[2004,1,15]]},"abstract":"<jats:p>Both imperatoxin A (IpTxa), a 33-residue peptide toxin from scorpion venom, and peptide A, derived from the II\u2013III loop of dihydropyridine receptor (DHPR), interact specifically with the skeletal ryanodine receptor (RyR1), which is a Ca2+-release channel in the sarcoplasmic reticulum, but with considerably different affinities. IpTxa activates RyR1 with nanomolar affinity, whereas peptide A activates RyR1 at micromolar concentrations. To investigate the molecular basis for high-affinity activation of RyR1 by IpTxa, we have determined the NMR solution structure of IpTxa, and identified its functional surface by using alanine-scanning analogues. A detailed comparison of the functional surface profiles for two peptide activators revealed that IpTxa exhibits a large functional surface area (approx. 1900 \u00c52, where 1 \u00c5=0.1 nm), based on a short double-stranded antiparallel \u03b2-sheet structure, while peptide A bears a much smaller functional surface area (approx. 800 \u00c52), with the five consecutive basic residues (Arg681, Lys682, Arg683, Arg684 and Lys685) being clustered at the C-terminal end of the \u03b1-helix. The functional surface of IpTxa is composed of six essential residues (Leu7, Lys22, Arg23, Arg24, Arg31 and Arg33) and several other important residues (His6, Lys8, Arg9, Lys11, Lys19, Lys20, Gly25, Thr26, Asn27 and Lys30), indicating that amino acid residues involved in RyR1 activation make up over the half of the toxin molecule with the exception of cysteine residues. Taken together, these results suggest that the site where peptide A binds to RyR1 belongs to a subset of macrosites capable of being occupied by IpTxa, resulting in differing the affinity and the mode of activation.<\/jats:p>","DOI":"10.1042\/bj20031192","type":"journal-article","created":{"date-parts":[[2004,1,12]],"date-time":"2004-01-12T10:01:33Z","timestamp":1073901693000},"page":"385-394","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Molecular basis of the high-affinity activation of type 1 ryanodine receptors by imperatoxin A"],"prefix":"10.1042","volume":"377","author":[{"given":"Chul Won","family":"LEE","sequence":"first","affiliation":[{"name":"Department of Life Science, Kwangju Institute of Science and Technology, Kwangju 500-712, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Hui","family":"LEE","sequence":"additional","affiliation":[{"name":"Department of Life Science, Kwangju Institute of Science and Technology, Kwangju 500-712, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koh","family":"TAKEUCHI","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"TAKAHASHI","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichio","family":"SHIMADA","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"SATO","sequence":"additional","affiliation":[{"name":"Department of Environmental Science, Fukuoka Women's University, Fukuoka 813-8529, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song Yub","family":"SHIN","sequence":"additional","affiliation":[{"name":"Research Center for Proteineous Materials, Chosun University, Kwangju 501-759, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Han","family":"KIM","sequence":"additional","affiliation":[{"name":"Department of Life Science, Kwangju Institute of Science and Technology, Kwangju 500-712, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Il","family":"KIM","sequence":"additional","affiliation":[{"name":"Department of Life Science, Kwangju Institute of Science and Technology, Kwangju 500-712, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/377\/2\/385\/712715\/bj3770385.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/377\/2\/385\/712715\/bj3770385.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T07:45:11Z","timestamp":1637567111000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/377\/2\/385\/40956\/Molecular-basis-of-the-high-affinity-activation-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,1,15]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2004,1,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj20031192","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,1,15]]}}}