{PDOC60028} {PS60028; SCORPION_CALCINE} {BEGIN} ************************************* * Scorpion calcine family signature * ************************************* Toxins of the scorpion calcine family bind directly to ryanodine receptors (RyRs), intracellular channel targets of the endoplasmic reticulum, and induce long lasting channel openings in a mode of smaller conductance. They have the ability to translocate into cells by crossing the plasma membrane [1-3]. Toxins of scorpion calcine family are highly basic 33-amino acid peptides that present three disulfide bridges (C1-C4, C2-C5, and C3-C6) and fold along a knottin or inhibitor cystine knot motif (see ) [1-3] [E1]. Their three dimensional structure consists of a compact disulfide-bonded core from which emerge loops and the N-terminus. The main element of regular secondary structure is a double-stranded antiparallel beta-sheet. A third peripheral extended strand is almost perpendicular to the double-stranded antiparallel beta-sheet [2,4]. Scorpion calcine mimic the activating segment of the dihydropyridine receptor II-III loop, which interacts with a region of the ryanodine receptor (see ) [1,2,5]. This family includes: - Imperatoxin-A (IpTx A) from Pandinus imperator (Emperor scorpion). - Opicalcin-1 and -2 from Opistophthalmus carinatus (African yellow leg scorpion). - Maurocalcin (MCa) from Scorpio maurus palmatus (Chactoid scorpion). We have developed a pattern that contains six conserved cysteines with a C-C-CC-C-C cysteine arrangement. -Conserved pattern: C-x(6)-C-x(5)-C-C-x(3)-C-x(9)-R-C [The 6 C's are involved in disulfide bonds] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Expert(s) to contact by email: Ramakumar S.; ramak@physics.iisc.ernet.in -Last update: February 2006 / First entry. [ 1] Gurrola G.B., Arevalo C., Sreekumar R., Lokuta A.J., Walker J.W., Valdivia H.H. "Activation of ryanodine receptors by imperatoxin A and a peptide segment of the II-III loop of the dihydropyridine receptor." J. Biol. Chem. 274:7879-7886(1999). PubMed=10075681 [ 2] Fajloun Z., Kharrat R., Chen L., Lecomte C., Di Luccio E., Bichet D., El Ayeb M., Rochat H., Allen P.D., Pessah I.N., De Waard M., Sabatier J.M. "Chemical synthesis and characterization of maurocalcine, a scorpion toxin that activates Ca(2+) release channel/ryanodine receptors." FEBS. Lett. 469:179-185(2000). PubMed=10713267 [ 3] Esteve E., Mabrouk K., Dupuis A., Smida-Rezgui S., Altafaj X., Grunwald D., Platel J.-C., Andreotti N., Marty I., Sabatier J.-M., Ronjat M., De Waard M. "Transduction of the scorpion toxin maurocalcine into cells. Evidence that the toxin crosses the plasma membrane." J. Biol. Chem. 280:12833-12839(2005). PubMed=15653689; DOI=10.1074/jbc.M412521200 [ 4] Mosbah A., Kharrat R., Fajloun Z., Renisio J.-G., Blanc E., Sabatier J.-M., El Ayeb M., Darbon H. "A new fold in the scorpion toxin family, associated with an activity on a ryanodine-sensitive calcium channel." Proteins 40:436-442(2000). PubMed=10861934; DOI=10.1002/1097-0134(20000815)40:3<436::AID-PROT90>3.0.CO;2-9 [ 5] Green D., Pace S., Curtis S.M., Sakowska M., Lamb G.D., Dulhunty A.F., Casarotto M.G. "The three-dimensional structural surface of two beta-sheet scorpion toxins mimics that of an alpha-helical dihydropyridine receptor segment." Biochem. J. 370:517-527(2003). PubMed=12429019; DOI=10.1042/BJ20021488 [E1] https://bioserv.cbs.cnrs.fr -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}