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8.B.16 The Membrance-pentitrating, Ryanodine Receptor-activating Maurocalcine (MaCa) Family

Maurocalcine (maurocalcin) (MCa) is a 33-amino acid residue peptide that was initially identified in the Tunisian scorpion, Scorpion maurus palmatus. This peptide triggers interest for three main reasons. First, it helps unravelling the mechanistic basis of Ca2+ mobilization from the sarcoplasmic reticulus because of its sequence homology with a calcium channel domain in excitation-contraction coupling. Second, it shows potent pharmacological properties because of its ability to activate the ryanodine receptor. Finally, it is of technological value because of its ability to carry cell-impermeable compounds across the plasma membrane. Mabrouk et al., 2007 characterized the molecular determinants that underlie the pharmacological and cell-penetrating properties of maurocalcin. They identify several key amino acid residues of the peptide that determine cell penetrability. Basic amino acid residues are required for an interaction with negatively charged lipids of the plasma membrane. Maurocalcine analogues that penetrate better have stronger interactions with negatively charged lipids.

This family belongs to the: Conotoxin Superfamily.

References associated with 8.B.16 family:

Dutertre, S., A.H. Jin, Q. Kaas, A. Jones, P.F. Alewood, and R.J. Lewis. (2013). Deep venomics reveals the mechanism for expanded peptide diversity in cone snail venom. Mol. Cell Proteomics 12: 312-329. 23152539
Fainzilber, M., T. Nakamura, J.C. Lodder, E. Zlotkin, K.S. Kits, and A.L. Burlingame. (1998). γ-Conotoxin-PnVIIA, a γ-carboxyglutamate-containing peptide agonist of neuronal pacemaker cation currents. Biochemistry 37: 1470-1477. 9484216
Fajloun, Z., R. Kharrat, L. Chen, C. Lecomte, E. Di Luccio, D. Bichet, M. El Ayeb, H. Rochat, P.D. Allen, I.N. Pessah, M. De Waard, and J.M. Sabatier. (2000). Chemical synthesis and characterization of maurocalcine, a scorpion toxin that activates Ca2+ release channel/ryanodine receptors. FEBS Lett. 469: 179-185. 10713267
Haji-Ghassemi, O., Y.S. Chen, K. Woll, G.B. Gurrola, C.R. Valdivia, W. Cai, S. Li, H.H. Valdivia, and F. Van Petegem. (2023). Cryo-EM analysis of scorpion toxin binding to Ryanodine Receptors reveals subconductance that is abolished by PKA phosphorylation. Sci Adv 9: eadf4936. 37224245
Mabrouk, K., N. Ram, S. Boisseau, F. Strappazzon, A. Rehaim, R. Sadoul, H. Darbon, M. Ronjat, and M. De Waard. (2007). Critical amino acid residues of maurocalcine involved in pharmacology, lipid interaction and cell penetration. Biochim. Biophys. Acta. 1768: 2528-2540. 17888395
Robinson, S.D. and R.S. Norton. (2014). Conotoxin gene superfamilies. Mar Drugs 12: 6058-6101. 25522317
Schwartz, E.F., E.M. Capes, E. Diego-García, F.Z. Zamudio, O. Fuentes, L.D. Possani, and H.H. Valdivia. (2009). Characterization of hadrucalcin, a peptide from Hadrurus gertschi scorpion venom with pharmacological activity on ryanodine receptors. Br J Pharmacol 157: 392-403. 19389159
Xiao, L., G.B. Gurrola, J. Zhang, C.R. Valdivia, M. SanMartin, F.Z. Zamudio, L. Zhang, L.D. Possani, and H.H. Valdivia. (2016). Structure-function relationships of peptides forming the calcin family of ryanodine receptor ligands. J Gen Physiol 147: 375-394. 27114612