ArticleThe Biochemical journal2003
The three-dimensional structural surface of two beta-sheet scorpion toxins mimics that of an alpha-helical dihydropyridine receptor segment.
Article in The Biochemical journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Exploring the Chemical Features and Biomedical Relevance of Cell-Penetrating Peptides.International journal of molecular sciences · 2024Review
- Scorpion venom components that affect ion-channels function.Toxicon : official journal of the International Society on Toxinology · 2013Review
- Cyclization of the intrinsically disordered α1S dihydropyridine receptor II-III loop enhances secondary structure and in vitro function.The Journal of biological chemistry · 2011Article
- Both basic and acidic amino acid residues of IpTx(a) are involved in triggering substate of RyR1.Journal of biomedicine & biotechnology · 2011Article
- Article
- Ubiquitous SPRY domains and their role in the skeletal type ryanodine receptor.European biophysics journal : EBJ · 2009Review
- Alternative splicing of RyR1 alters the efficacy of skeletal EC coupling.Cell calcium · 2009Article
- Hemicalcin, a new toxin from the Iranian scorpion Hemiscorpius lepturus which is active on ryanodine-sensitive Ca2+ channels.The Biochemical journal · 2007Article
- Transient loss of voltage control of Ca2+ release in the presence of maurocalcine in skeletal muscle.Biophysical journal · 2006Article
- Novel regulators of RyR Ca2+ release channels: insight into molecular changes in genetically-linked myopathies.Journal of muscle research and cell motility · 2006Review
- Differential effects of maurocalcine on Ca2+ release events and depolarization-induced Ca2+ release in rat skeletal muscle.The Journal of physiology · 2005Article
- Functional implications of modifying RyR-activating peptides for membrane permeability.British journal of pharmacology · 2005Article
- Maurocalcine and domain A of the II-III loop of the dihydropyridine receptor Cav 1.1 subunit share common binding sites on the skeletal ryanodine receptor.The Journal of biological chemistry · 2005Article
- Peptide fragments of the dihydropyridine receptor can modulate cardiac ryanodine receptor channel activity and sarcoplasmic reticulum Ca2+ release.The Biochemical journal · 2004Article
- Molecular basis of the high-affinity activation of type 1 ryanodine receptors by imperatoxin A.The Biochemical journal · 2004Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.