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Crystal Structure of a CRISP Family Ca2+-channel Blocker Derived from Snake Venom

Authors :
Shikamoto, Yasuo
Suto, Kyoko
Yamazaki, Yasuo
Morita, Takashi
Mizuno, Hiroshi
Source :
Journal of Molecular Biology. Jul2005, Vol. 350 Issue 4, p735-743. 9p.
Publication Year :
2005

Abstract

The cysteine-rich secretory proteins (CRISPs) are widely distributed in mammals, reptiles, amphibians and secernenteas, and are involved in a variety of biological reactions. Here we report the crystal structure of triflin, a snake venom derived blocker of high K+-induced artery contraction, at 2.4Å resolution. Triflin consists of two domains. The first 163 residues form a large globular body with an α–β–α sandwich core, which resembles pathogenesis-related proteins of group-1 (PR-1). Two glutamic acid-associated histidine residues are located in an elongated cleft. A Cd2+ resides in this binding site, and forms a five-coordination sphere. The subsequent cysteine-rich domain adopts a rod-like shape, which is stabilized by five disulfide bridges. Hydrophobic residues, which may obstruct the target ion-channel, are exposed to the solvent. A concave surface, which is surrounded by these two domains, is also expected to play a significant role in the binding to the target receptor, leading to ion channel blockage. The C-terminal cysteine-rich region has a similar tertiary structure to voltage-gated potassium channel blocker toxins, such as BgK and ShK. These findings will contribute toward understanding the functions of the widely distributed CRISP family proteins. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
00222836
Volume :
350
Issue :
4
Database :
Academic Search Index
Journal :
Journal of Molecular Biology
Publication Type :
Academic Journal
Accession number :
18091241
Full Text :
https://doi.org/10.1016/j.jmb.2005.05.020