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Journal of Biochemistry Advance Access originally published online on December 23, 2008
Journal of Biochemistry 2009 145(3):365-375; doi:10.1093/jb/mvn174
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© The Authors 2008. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved

Structural Divergence of Cysteine-Rich Secretory Proteins in Snake Venoms{dagger}

Yukiko Matsunaga1, Yasuo Yamazaki1, Fumiko Hyodo1, Yusuke Sugiyama1, Masatoshi Nozaki2 and Takashi Morita1,*

1Department of Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588; and 2Okinawa Prefectural Institute of Health and Environment, 2003 Ozato, Ozato, Nanjo, Okinawa 901-1202, Japan

*To whom correspondence should be addressed. E-mail: tmorita{at}my-pharm.ac.jp

Received October 31, 2008; Accepted December 9, 2008


   Abstract

Cysteine-rich secretory proteins (CRISPs) are expressed in spermatocytes and granules of neutrophils in mammals, and are associated with sperm maturation and host defense. Related proteins have recently been recovered in snake venoms, and some of the snake venom-derived CRISPs exhibit ion channel blocking activity. Here we isolated and identified two novel CRISPs (kaouthin-1 and kaouthin-2) from the venom of Naja kaouthia (Elapidae), and cloned the encoding cDNAs. Kaouthin-1 and kaouthin-2 were classified into two broad sister groups of Elapidae, the Asian species and the marine/Australian species, respectively. Sequence comparisons reveal that the high-frequency variable regions among snake venom CRISPs define a continuous line on the molecular surface of the N-terminal pathogenesis-related protein-1 (PR-1) domain and the C-terminal cysteine-rich domain (CRD). Snake venom proteins generally display efficient molecular diversity around functionally key regions, suggesting that the PR-1 domain of CRISPs is important for the recognition of target molecules.

Key Words: CRISP, Naja kaouthia, pathogenesis-related protein, cysteine-rich domain, ion channel

Abbreviations: CNG, cyclic nucleotide-gated; CRD, cysteine-rich domain; CRISP, cysteine-rich secretory protein; ELISA, enzyme-linked immunosorbent assay; PR-1, pathogenesis-related protein 1; PsTx, pseudechetoxin; RACE, rapid amplification of cDNA ends


{dagger}Nucleotide sequence data reported are available in the GenBank databases under the accession numbers, EU938339 [GenBank] and EU938340.


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