Crystal structure of the cysteine-rich secretory protein stecrisp reveals that the cysteine-rich domain has a K+ channel inhibitor-like fold

被引:127
作者
Guo, M
Teng, MK
Niu, LW
Liu, Q
Huang, QQ
Hao, Q
机构
[1] Univ Sci & Technol China, Key Lab Struct Biol, Chinese Acad Sci, Dept Mol & Cell Biol,Sch Life Sci,Hefei Natl Lab, Hefei 230026, Anhui, Peoples R China
[2] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA
关键词
D O I
10.1074/jbc.M413566200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:12405 / 12412
页数:8
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