8dtb

Structural highlights

Function

CAIMP_PANIM This toxin affects the activity of ryanodine receptors 1, 2 and 3 (RyR1, RyR2 and RyR3) (PubMed:1334561, PubMed:9565405, PubMed:11867448). At lower concentrations the toxin increases full openings of the RyRs, and at higher concentrations it inhibits full openings and induces openings to subconductance levels (30% of the full conductance state) and reduces the number of full conductance openings (PubMed:9565405, PubMed:27114612). The different actions may be attributed to the toxins binding at different sites on the RyRs, with binding at a high-affinity site mediating the increase in full openings and the induction of subconductance states evoked upon binding to a lower-affinity site (PubMed:14699105). Furthermore, it triggers calcium release from sarcoplasmic vesicles (11.7 nM are enough to induce a sharp release, and 70% of the total calcium is released after toxin (100 nM) addition) probably by acting as a cell-penetrating peptide (CPP) (PubMed:1334561, PubMed:27114612). In addition, it has been shown to dose-dependently stimulate ryanodine binding to RyR1 (EC(50)=8.7 nM) (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:9565405). It acts synergistically with caffeine (By similarity). In vivo, intracerebroventricular injection into mice induces neurotoxic symptoms, followed by death (By similarity).[UniProtKB:A0A1L4BJ42][UniProtKB:B8QG00][UniProtKB:P60254]^{[1] [2] [3] [4]}

References

1. ↑ Nabhani T, Zhu X, Simeoni I, Sorrentino V, Valdivia HH, Garcia J. Imperatoxin a enhances Ca(2+) release in developing skeletal muscle containing ryanodine receptor type 3. Biophys J. 2002 Mar;82(3):1319-28. PMID:11867448 doi:http://dx.doi.org/10.1016/S0006-3495(02)75487-8
2. ↑ Valdivia HH, Kirby MS, Lederer WJ, Coronado R. Scorpion toxins targeted against the sarcoplasmic reticulum Ca(2+)-release channel of skeletal and cardiac muscle. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12185-9. PMID:1334561 doi:10.1073/pnas.89.24.12185
3. ↑ Dulhunty AF, Curtis SM, Watson S, Cengia L, Casarotto MG. Multiple actions of imperatoxin A on ryanodine receptors: interactions with the II-III loop "A" fragment. J Biol Chem. 2004 Mar 19;279(12):11853-62. Epub 2003 Dec 29. PMID:14699105 doi:http://dx.doi.org/10.1074/jbc.M310466200
4. ↑ Tripathy A, Resch W, Xu L, Valdivia HH, Meissner G. Imperatoxin A induces subconductance states in Ca2+ release channels (ryanodine receptors) of cardiac and skeletal muscle. J Gen Physiol. 1998 May;111(5):679-90. PMID:9565405