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Identification of the B Subtype of γ-Phospholipase A2 Inhibitor from Protobothrops flavoviridis Serum and Molecular Evolution of Snake Serum Phospholipase A2 Inhibitors

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Abstract

A cDNA encoding a novel phospholipase A2 (PLA2) inhibitor (PLI) was isolated from a Protobothrops flavoviridis snake (Tokunoshima island, Japan) liver cDNA library. This cDNA encoded a signal peptide of 19 amino acids followed by a mature protein of 181 amino acids. Its N-terminal amino acid sequence was completely in accord with that of a PLI, named PLI-II, previously found in P. flavoviridis serum. PLI-II showed a high similarity in sequence to the B subtype of γPLI, denoted γPLI-B, isolated from Agkistrodon blomhoffii siniticus serum. Thus, PLI-II is P. flavoviridis serum γPLI-B. Since PLI-I, previously isolated from P. flavoviridis serum, can be assigned as γPLI-A, P. flavoviridis serum contains both A and B subtypes of γPLI. Phylogenetic analysis of γPLIs from the sera of various kinds of snakes, Elapinae, Colubrinae, Laticaudinae, Acanthophiinae, Crotalinae, and Pythonidae, based on the amino acid sequences revealed that A and B subtypes of γPLIs are clearly separated from each other. It was also found that phylogenetic topologies of γPLIs are in good agreement with speciation processes of snakes. The BLAST search followed by analyses with particular Internet search engines of proteins with Cys/loop frameworks similar to those of PLI-II and PLI-I revealed that γPLI-Bs, including PLI-II and PLI-II-like proteins from mammalian sources, form a novel PLI-II family which possesses the common Cys/loop frameworks in the anterior and posterior three-finger motifs in the molecules. Several lines of evidence suggest that PLI-II is evolutionarily ancestral to PLI-I.

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Acknowledgment

This work was supported in part by Grants-in Aid for Young Scientists under category “A” for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (T.C.).

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Authors and Affiliations

  1. Department of Applied Life Science, Faculty of Bioscience and Biotechnology, Sojo University, 4-22-1 Ikeda, Kumamoto, 860-0082, Japan

    Shuhei So, Takahito Chijiwa, Naoki Ikeda & Motonori Ohno

  2. Division of Cell Fate Modification, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto, 860-0811, Japan

    Ikuo Nobuhisa

  3. Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto, 860-0082, Japan

    Naoko Oda-Ueda

  4. Institute of Medical Science, University of Tokyo, Oshima-gun, Kagoshima, 894-1531, Japan

    Shosaku Hattori

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  1. Shuhei So
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  2. Takahito Chijiwa
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  3. Naoki Ikeda
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  4. Ikuo Nobuhisa
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  7. Motonori Ohno
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Correspondence to Takahito Chijiwa.

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The nucleotide sequence reported in this paper is available from the GenBank/EMBL/DDBJ databases under accession number AB290845.

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So, S., Chijiwa, T., Ikeda, N. et al. Identification of the B Subtype of γ-Phospholipase A2 Inhibitor from Protobothrops flavoviridis Serum and Molecular Evolution of Snake Serum Phospholipase A2 Inhibitors. J Mol Evol 66, 298–307 (2008). https://doi.org/10.1007/s00239-008-9089-1

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