Imperatoxin a

Imperatoxin A (IpTxa) is a peptide which increases Ryanodine binding to Ryanodine receptor (RyR) and by doing so enhances the influx of Ca2+ from the sarcoplasmatic reticulum into the cell.

Source

The toxin comes from the venom of the African scorpion "Pandinus imperator".

[cite journal |author=Valdivia HH, Kirby MS, Lederer Coronado R
title= Scorpion toxins targeted against the sarcoplasmic reticulum Ca(2+)-release channel of skeletal and cardiac muscle. |journal=Proc. Natl. Acad. Sci. |volume=89 |pages=12185-12189|year=1992 |pmid= 1334561 |url=http://www.ncbi.nlm.nih.gov/pubmed/ 1334561

]

Chemistry

The structure of IpTxi
- 33 amino acids peptide.
- shares the structure and function of the dihydropiridine receptor (DHPR). It corresponds to the II-III loop of the α1s subunit.
- three cysteine residues that form disulfide bridges to stabilize the three dimensional structure.

Molecular weight

The molecular weight of the toxin is 3.7 kDa.

Target

IpTxa acts on the Ryanodine receptors (RyR), these are intracellular Ca2+ release channels mainly known for their role in regulating Ca2+ release from the sarcoplasmatic reticulum of striated muscles [cite journal |author=Franzini/Armstrong C, Protasi F |title= Ryanodine receptors of striated muscles: a complex channel capable of multiple interactions. |journal=Physiol. Rev. |volume=77 |issue=3 |pages=699-729 |year=1997 |pmid= 9234963 |url=http://www.ncbi.nlm.nih.gov/pubmed/9234963

] . The peptide acts better on RyR type 1 than on type 3. RyR 2 seems to be insensitive to IpTxa. [cite journal |author=Simeoni I, Rossi D, Zhu X, García J, Vadivia HH, Sorrentino V |title= Imperatoxin A (IpTx(a)) from Pandinus imperator stimulates [(3)H] ryanodine binding to RyR3 channels. |journal=FEBS Letters |issue=508 |pages=5-10 |year=2001 |pmid= 11707258 |url=http://www.ncbi.nlm.nih.gov/pubmed/11707258

]

Mode of action

The part of the peptide that looks like the II-III loop of the (DHPR) binds directly to RyR and enhance ryanodine binding to trigger Ca2+ release. [cite journal |author=Simeoni I, Rossi D, Zhu X, García J, Vadivia HH, Sorrentino V |title= Imperatoxin A (IpTx(a)) from Pandinus imperator stimulates [(3)H] ryanodine binding to RyR3 channels. |journal=FEBS Letters |issue=508 |pages=5-10 |year=2001 |pmid= 11707258 |url=http://www.ncbi.nlm.nih.gov/pubmed/11707258

]

References

reflist