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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
Pt 2
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pubmed:dateCreated |
2003-2-19
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pubmed:databankReference |
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pubmed:abstractText |
An alpha-helical II-III 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 beta-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 alpha-helical dihydropyridine receptor segment. We increased the alignment of basic residues in the alpha-helical peptide to mimic the spatial orientation of active residues in the scorpion toxin, with a consequent 2-20-fold increase in the activity of the alpha-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 alpha-helical peptide and the beta-sheet toxin, a 10-100-fold reduction in channel closed time, with a < or = 2-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.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-10075681,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-10346894,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-10359078,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-10388749,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-10427100,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-10571252,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-10713267,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-10766780,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-10861934,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-11251053,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-11258936,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-11259290,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-11320225,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-11323714,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-11371447,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-11509356,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-1490109,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-1960729,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-2165570,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-3459158,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-6661238,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-7417242,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-7523191,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-7673188,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-7921673,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-8994600,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-9525869,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-9565405,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12429019-9578589
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0264-6021
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
370
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
517-27
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:12429019-Animals,
pubmed-meshheading:12429019-Calcium,
pubmed-meshheading:12429019-Calcium Channels, L-Type,
pubmed-meshheading:12429019-Magnetic Resonance Spectroscopy,
pubmed-meshheading:12429019-Muscle Fibers, Skeletal,
pubmed-meshheading:12429019-Peptides,
pubmed-meshheading:12429019-Protein Structure, Secondary,
pubmed-meshheading:12429019-Rats,
pubmed-meshheading:12429019-Ryanodine Receptor Calcium Release Channel,
pubmed-meshheading:12429019-Scorpion Venoms
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pubmed:year |
2003
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pubmed:articleTitle |
The three-dimensional structural surface of two beta-sheet scorpion toxins mimics that of an alpha-helical dihydropyridine receptor segment.
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pubmed:affiliation |
Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, P.O. Box 334, Canberra, ACT, 2601, Australia.
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pubmed:publicationType |
Journal Article
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