Determination of Disulfide Bond Connectivity of Cysteine-rich Peptide IpTx_a

摘要

Disulfide bonds play a crucial role in the folding and structural stabilization of many important extracellular peptides and proteins including hormones, enzymes, growth factors, toxins, and immunoglobulins. Cysteine-rich peptides stabilized by intramolecular disulfide bonds have often been isolated from venoms of microbes, animals and plants. These peptides typically have much higher stability and improved biopharmaceutical properties compared to their linear counterparts. Therefore the correct disulfide bond formation of small proteins and peptides has been extensively studied for a better understanding of their folding mechanism and achieving efficient generation of the naturally occurring biologically active product. Imperatoxin A (IpTx_a), a peptide toxin containing 6 cysteine residues, was isolated from the venom of scorpion Pandinus imperator, selectively binds the ryanodine receptors and activates Ca~(2+) release from sarcoplasmic reticulum (SR). IpTx_a increases the binding of ryanodine to ryanodine receptors (RyRs) and encourages reconstituted single channel to induce subconductance states.