3D STRUCT OF IMPERATOXIN A, PEPTIDE LIGAND OF CA2+ RELEASE CHANNELS

心脏和骨骼肌外膜的去极化 肌肉导致从细胞内储存的Ca 2+释放， 扭转，弹性收缩。 外部电压传感器 膜是二氢吡啶受体（DHPR）和蛋白质 负责Ca 2+释放的是Ca 2+释放通道， 肌浆网，也称为ryanodine受体（RyR）。 DHPR打开RyR并引起收缩的机制是 未知，但最近的研究结果表明，一个特定的部分， DHPR可以直接连接到RyR。 Imperatoxin A（IpTxa），a 33 以高亲和力打开RyR的氨基酸蝎毒素， 提供了有关参与的确切氨基酸的信息， DHPR和RyR之间的相互作用和反应的性质 涉案 IpTxa的结合被22个氨基酸取代， DHPR的片段以及IpTxa和DHPR片段都失去了它们的 当Thr（在IpTxa中）或Ser（在DHPR中） 被带负电荷的氨基酸取代。 因此，IpTxa打开Ryr， 类似于天然DHPR-RyR相互作用的方式。 IpTxa的三维结构的阐明将增加 这对我们理解DHPR如何与RyR相互作用有重要意义。

Depolarization of the external membrane of cardiac and skeletal muscle results in release of Ca2+ from intracellular stores, which in turn, elicits contraction. The voltage sensor of the external membrane is the dihydropyridine receptor (DHPR) and the protein responsible for Ca2+ release is the Ca2+ release channel of sarcoplasmic reticulum, also know as the ryanodine receptor (RyR). The mechanism by which DHPRs open RyR and elicit contraction is unknown, but recent findings suggest that a specific segment of the DHPR may be directly connected to RyR. Imperatoxin A (IpTxa), a 33 amino acid scorpion toxin that opens RyR with high affinity, may provide information regarding the exact amino acids involved in the interaction between DHPR and RyR and the nature of the reaction involved. The binding of IpTxa is displaced by a 22 amino acid segment of the DHPR and both, IpTxa and the DHPR segment loose their capacity to open RyR when a Thr (in IpTxa) or Ser (in DHPR) is replaced by a negatively-charged amino acid. Thus, IpTxa open Ryr in a manner which is similar to the natural DHPR-RyR interaction. Elucidation of the three-dimensional structure of IpTxa will add significantly to our understanding of how DHPR interacts with RyR.