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

心脏和骨骼外膜的去极化 肌肉导致细胞内储存的钙释放，这在 转身，引起收缩。外置电压传感器 膜是二氢吡啶受体(DHPR)和蛋白质 负责钙离子释放的是钙离子释放通道 肌浆网，也称为兰尼定受体(RyR)。 DHPR开放RyR并引起收缩的机制是 未知，但最近的发现表明，特定的片段 DHPR可能与RyR直接相连。小蜂毒素A(Imperatoxin A，IpTxa)，33 氨基酸蝎子毒素以高亲和力打开RyR，可能 提供有关参与的确切氨基酸的信息 DHPR与RyR的相互作用及反应性质 牵涉其中。IpTxa的结合被22个氨基酸取代 DHPR段和两者，IpTxa和DHPR段松动 当THR(在IpTxa中)或Ser(在DHPR中)为时打开RyR的能力 被带负电荷的氨基酸取代。因此，IpTxa打开RyR in 一种类似于DHPR-RyR自然相互作用的方式。 对IpTxa三维结构的阐明将增加 对我们理解DHPR与RyR的相互作用具有重要意义。

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.