1c6w

Structural highlights

Function

CAMAU_SCOPA This toxin stabilizes ryanodine receptor 1 (RyR1) opening in a long-lasting subconductance state (48%-60% of the full conductance state) (PubMed:10713267, PubMed:12869557, PubMed:27114612). Furthermore, it triggers calcium release from sarcoplasmic vesicles (6.6 nM are enough to induce a sharp release, and 60% of the total calcium is released after toxin (100 nM) addition) probably by acting as a cell-penetrating peptide (CPP) (PubMed:27114612). In addition, it has been shown to dose-dependently stimulate ryanodine binding to RyR1 (EC(50)=12.5-26.4 nM) (PubMed:12869557, PubMed:17291197, PubMed:17888395, PubMed:27114612). It also augments the bell-shaped calcium-[3H]ryanodine binding curve that is maximal at about 10 uM calcium concentration (PubMed:27114612). It binds a different site as ryanodine (PubMed:10713267). It acts synergistically with caffeine (By similarity). In vivo, intracerebroventricular injection into mice causes death (PubMed:10713267).[UniProtKB:A0A1L4BJ42][UniProtKB:B8QG00][UniProtKB:P59868]^{[1] [2] [3] [4] [5]}

References

1. ↑ Fajloun Z, Kharrat R, Chen L, Lecomte C, Di Luccio E, Bichet D, El Ayeb M, Rochat H, Allen PD, Pessah IN, De Waard M, Sabatier JM. Chemical synthesis and characterization of maurocalcine, a scorpion toxin that activates Ca(2+) release channel/ryanodine receptors. FEBS Lett. 2000 Mar 10;469(2-3):179-85. PMID:10713267 doi:10.1016/s0014-5793(00)01239-4
2. ↑ Estève E, Smida-Rezgui S, Sarkozi S, Szegedi C, Regaya I, Chen L, Altafaj X, Rochat H, Allen P, Pessah IN, Marty I, Sabatier JM, Jona I, De Waard M, Ronjat M. Critical amino acid residues determine the binding affinity and the Ca2+ release efficacy of maurocalcine in skeletal muscle cells. J Biol Chem. 2003 Sep 26;278(39):37822-31. PMID:12869557 doi:10.1074/jbc.M305798200
3. ↑ Shahbazzadeh D, Srairi-Abid N, Feng W, Ram N, Borchani L, Ronjat M, Akbari A, Pessah IN, De Waard M, El Ayeb M. Hemicalcin, a new toxin from the Iranian scorpion Hemiscorpius lepturus which is active on ryanodine-sensitive Ca2+ channels. Biochem J. 2007 May 15;404(1):89-96. PMID:17291197 doi:10.1042/BJ20061404
4. ↑ Mabrouk K, Ram N, Boisseau S, Strappazzon F, Rehaim A, Sadoul R, Darbon H, Ronjat M, De Waard M. Critical amino acid residues of maurocalcine involved in pharmacology, lipid interaction and cell penetration. Biochim Biophys Acta. 2007 Oct;1768(10):2528-40. PMID:17888395 doi:10.1016/j.bbamem.2007.06.030
5. ↑ Xiao L, Gurrola GB, Zhang J, Valdivia CR, SanMartin M, Zamudio FZ, Zhang L, Possani LD, Valdivia HH. Structure-function relationships of peptides forming the calcin family of ryanodine receptor ligands. J Gen Physiol. 2016 May;147(5):375-94. PMID:27114612 doi:10.1085/jgp.201511499
6. ↑ Mosbah A, Kharrat R, Fajloun Z, Renisio JG, Blanc E, Sabatier JM, El Ayeb M, Darbon H. A new fold in the scorpion toxin family, associated with an activity on a ryanodine-sensitive calcium channel. Proteins. 2000 Aug 15;40(3):436-42. PMID:10861934