Crystal structure of the cysteine-rich secretory protein stecrisp reveals that the cysteine-rich domain has a K+ channel inhibitor-like fold
Crystal structure of the cysteine-rich secretory protein stecrisp reveals that the cysteine-rich domain has a K+ channel inhibitor-like fold
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DOI：
10.1074/jbc.m413566200
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发表时间：
2005-04-01
影响因子：
4.8
通讯作者：
Hao, Q
中科院分区：
文献类型：
--
作者：
Guo, M;Teng, MK;Hao, Q
竹叶青蛇（Trimeresurusstejnegeri）蛇毒中的Stecrisp蛋白属于富含半胱氨酸的分泌蛋白（CRISP）家族，具有多种与精卵融合、宿主防御和离子通道阻断相关的功能。在这里，我们提出了晶体结构的精细到1.6埃的分辨率。结果表明，stecris包含三个区域，即PR-1（组1的发病机制相关蛋白）结构域，铰链和富含半胱氨酸的结构域（CRD）。PR-1结构域中暴露于溶剂的保守残基（His（60）、Glu（75）、Glu（96）和His（115））的构象与其同源结构中的对应物的构象相似，表明它们可能共享某些分子机制。PR-1结构域中可能的底物结合位点周围的高变序列的三个柔性环在同源结构中显示出明显的差异，这意味着物种和底物特异性相互作用的多样性可能参与识别和催化。铰链通过两个交叉的二硫键固定，所述二硫键由羧基末端区域中的十个特征性半胱氨酸中的四个形成，并且对于稳定N末端PR-1结构域是重要的。CRD与PR-1结构域在空间上分离，与两种K+通道抑制剂（Bgk和Shk）具有相似的折叠。离子通道阻断的可能功能位点的几个候选者位于CRD中的溶剂暴露环中。stecrips的结构将为CRISP家族不同成员的结构和功能探索提供原型架构。
Stecrisp from Trimeresurus stejnegeri snake venom belongs to a family of cysteine-rich secretory proteins ( CRISP) that have various functions related to sperm-egg fusion, innate host defense, and the blockage of ion channels. Here we present the crystal structure of stec-risp refined to 1.6-angstrom resolution. It shows that stecrisp contains three regions, namely a PR-1 (pathogenesis-related proteins of group1) domain, a hinge, and a cysteine-rich domain (CRD). A conformation of solvent-exposed and -conserved residues (His(60), Glu(75), Glu(96), and His(115)) in the PR-1 domain similar to that of their counterparts in homologous structures suggests they may share some molecular mechanism. Three flexible loops of hypervariable sequence surrounding the possible substrate binding site in the PR-1 domain show an evident difference in homologous structures, implying that a great diversity of species- and substrate-specific interactions may be involved in recognition and catalysis. The hinge is fixed by two crossed disulfide bonds formed by four of ten characteristic cysteines in the carboxyl-terminal region and is important for stabilizing the N-terminal PR-1 domain. Spatially separated from the PR-1 domain, CRD possesses a similar fold with two K+ channel inhibitors (Bgk and Shk). Several candidates for the possible functional sites of ion channel blocking are located in a solvent-exposed loop in the CRD. The structure of stecrisp will provide a prototypic architecture for a structural and functional exploration of the diverse members of the CRISP family.