title: Crystal structure of a CRISP family Ca2+ -channel blocker derived from snake venom.
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 2.4A resolution. Triflin consists of two domains. The first 163 residues form a large globular body with an alpha-beta-alpha 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 Cd(2+) 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.
authors.affiliation: Department of Biochemistry, National Institute of Agrobiological Sciences, Kannondai 2-1-2, Tsukuba, Ibaraki 305-8602, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shikamoto
authors.forename: Kyoko
authors.initials: K
authors.lastname: Suto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Morita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizuno
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D003435:Crotalid Venoms / Q000737:chemistry* / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D017841:Trimeresurus
chemical_list: D002121:Calcium Channel Blockers; D003435:Crotalid Venoms; C029748:Trimeresurus venoms; C502756:triflin protein, Trimeresurus flavoviridis