Molecular Evolution of Snake Toxins: Is the Functional Diversify of Snake Toxins Associated with a Mechanism of Accelerated Evolution?

Ohno, Motonori; Ménez, R.; Ogawa, Tomoya; Danse, Jean-Marc; Shimohigashi, Yasuyuki; Fromen, Catherine A.; Ducancel, Frédéric; Zinn‐Justin, Sophie; Du, M.H. Le; Boulain, Jean‐Claude; Tamiya, Tôru; Ménèz, Andre

doi:10.1016/s0079-6603(08)61036-3

Cited by 195 publications

(131 citation statements)

References 185 publications

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“…Thus, except for these proteins, all of which were found in the pooled venoms (Table 2), the peptide mass fingerprinting approach alone was unable to identify any protein in the databases. In addition, as expected from the rapid amino acid sequence divergence of venom proteins evolving under accelerated evolution, [50][51][52][53][54][55][56] with a few exceptions, the product ion spectra did not match any known protein. Hence, mass spectra were manually interpreted for de novo sequencing and the CID-MS/ MS-deduced peptide ion sequences (Table 2) were submitted to BLAST similarity searches.…”

Section: Results and Discusionmentioning

confidence: 99%

Snake Venomics of the Lancehead Pitviper Bothrops asper: Geographic, Individual, and Ontogenetic Variations

et al. 2008

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We report the comparative proteomic characterization of the venoms of adult and newborn specimens of the lancehead pitviper Bothrops asper from two geographically isolated populations from the Caribbean and the Pacific versants of Costa Rica. The crude venoms were fractionated by reverse-phase HPLC, followed by analysis of each chromatographic fraction by SDS-PAGE, N-terminal sequencing, MALDI-TOF mass fingerprinting, and collision-induced dissociation tandem mass spectrometry of tryptic peptides. The two B. asper populations, separated since the late Miocene or early Pliocene (8-5 mya) by the Guanacaste Mountain Range, Central Mountain Range, and Talamanca Mountain Range, contain both identical and different (iso)enzymes from the PLA 2 , serine proteinase, and SVMP families. Using a similarity coefficient, we estimate that the similarity of venom proteins between the two B. asper populations may be around 52%. Compositional differences between venoms among different geographic regions may be due to evolutionary environmental pressure acting on isolated populations. To investigate venom variability among specimens from the two B. asper populations, the reverse-phase HPLC protein profiles of 15 venoms from Caribbean specimens and 11 venoms from snakes from Pacific regions were compared. Within each B. asper geographic populations, all major venom protein families appeared to be subjected to individual variations. The occurrence of intraspecific individual allopatric variability highlights the concept that a species, B. asper in our case, should be considered as a group of metapopulations. Analysis of pooled venoms of neonate specimens from Caribbean and Pacific regions with those of adult snakes from the same geographical habitat revealed prominent ontogenetic changes in both geographical populations. Major ontogenetic changes appear to be a shift from a PIII-SVMP-rich to a PI-SVMP-rich venom and the secretion in adults of a distinct set of PLA 2 molecules than in the neonates. In addition, the ontogenetic venom composition shift results in increasing venom complexity, indicating that the requirement for the venom to immobilize prey and initiate digestion may change with the size (age) of the snake. Besides ecological and taxonomical implications, the geographical venom variability reported here may have an impact in the treatment of bite victims and in the selection of specimens for antivenom production. The occurrence of intraspecies variability in the biochemical composition and symptomatology after envenomation by snakes from different gegraphical location and age has long been apreciated by herpetologist and toxinologists, though detailed comparative proteomic analysis are scarce. Our study represents the first detailed characterization of individual and ontogenetic venom protein profile variations in two geographical isolated B. asper populations, and highlights the necessity of using pooled venoms as a statistically representative venom for antivenom production.

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Section: Results and Discusionmentioning

confidence: 99%

Snake Venomics of the Lancehead Pitviper Bothrops asper: Geographic, Individual, and Ontogenetic Variations

et al. 2008

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“…Polymorphic PLA 2 genes and mRNAs are usually found in snake venom glands [25]. Six of the 10 C. rhodostoma PLA 2 clones are apparently not translated into venom proteins.…”

Section: Untranslated Pla 2 Mrnasmentioning

confidence: 99%

Phospholipases A₂ from Callosellasma rhodostoma venom gland

Tsai

Wang

et al. 2000

European Journal of Biochemistry

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Callosellasma rhodostoma (Malayan pitviper) is a monotypic Asian pitviper of medical importance. Three acidic phospholipases A 2 (PLA 2 s) and one basic PLA 2 -homolog were purified from its venom while 10 cDNAs encoding distinct PLA 2 s were cloned from venom glands of a Thailand specimen of this species. Complete amino-acid sequences of the purified PLA 2 s were successfully deduced from their cDNA sequences. Among the six un-translated PLA 2 cDNAs, two apparently result from recombination of its Lys49-PLA 2 gene with its Asp49-PLA 2 genes. The acidic PLA 2 s inhibit platelet-aggregation, while the noncatalytic PLA 2 -homolog induces local edema. This basic PLA 2 -homolog contains both Asp49 and other, unusual substitutions unique for the venom Lys49-PLA 2 subtype (e.g. Leu5, Trp6, Asn28 and Arg34). Three-dimensional modelling of the basic protein revealed a heparin-binding region, and an abnormal calcium-binding pocket, which may explain its low catalytic activity. Oxidation of up to six of its Met residues or coinjection with heparin reduced its edemainducing activity but methylation of its active site His48 did not. The distinct Arg/Lys-rich and Met-rich region at positions 10±36 of the PLA 2 homolog presumably are involved in its heparin-binding and the cell membraneinterference leading to edema and myotoxicity.

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“…Peptide toxins from venomous creatures have served as vital tools to define the molecular mechanisms underlying K ϩ channel function (1,2). It has been suggested that toxins evolved from endogenous genes that function in normal cellular pathways (3,4). Indeed, venomous creatures possess toxins with homology to several proteins, including acetylcholinesterases (5), phospholipases (6,7), nerve growth factor (8), endothelins (9), Lynx-1 (10,11), Kunitz-type serine protease inhibitors (12), and the ion channel regulatory (ICR) 5 domains of cysteinerich secretory proteins (CRISPs) (3,13,14).…”

mentioning

confidence: 99%

Potassium Channel Modulation by a Toxin Domain in Matrix Metalloprotease 23

Rangaraju

Khoo

Feng

et al. 2010

Journal of Biological Chemistry

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Mechanisms that fine tune the activity of potassium channels are crucial to a cell's ability to integrate and respond to a plethora of internal and external signals. Peptide toxins from venomous creatures have served as vital tools to define the molecular mechanisms underlying K ϩ channel function (1, 2). It has been suggested that toxins evolved from endogenous genes that function in normal cellular pathways (3, 4). Indeed, venomous creatures possess toxins with homology to several proteins, including acetylcholinesterases (5), phospholipases (6, 7), nerve growth factor (8), endothelins (9), Lynx-1 (10, 11), Kunitz-type serine protease inhibitors (12), and the ion channel regulatory (ICR) 5 domains of cysteinerich secretory proteins (CRISPs) (3,13,14). Mammalian proteins containing toxin-like domains (TxDs) that block K ϩ channels have not been characterized previously.BgK, a 37-residue peptide toxin from the sea anemone Bunodosoma granulifera (15,16), and ShK, a 35-residue peptide toxin from the sea anemone Stichodactyla helianthus (17,18) are potent inhibitors of K ϩ channels. The Simple Modular Architecture Research Tool (SMART) (available on the World Wide Web) predicts the existence of a large superfamily of proteins that contain domains (referred to as ShKT domains in the SMART data base) resembling these two toxins (Fig. 1A). Many of these proteins (ϳ70 proteins) are metallopeptidases, whereas others are prolyl-4-hydroxylases, tyrosinases, peroxidases, oxidoreductases, or proteins containing epidermal growth factor-like domains, thrombospondin-type repeats, or trypsin-like serine protease domains (Fig. 1B). The only human protein containing a ShKT domain in the SMART data base is MMP23 (matrix metalloprotease 23). Matrix metalloproteases belong to the metzincin superfamily and play important roles in tissue remodeling, development, and the immune response (19).MMP23 is expressed in many tissues and exists either as a type II transmembrane protein in ER/nuclear membranes or as a secreted form following cleavage of the RRRRY motif just N-terminal to the Zn 2ϩ -dependent metalloprotease domain (20 -23). The ShKT domain of MMP23 (MMP23 TxD ) lies between the metalloprotease domain and an immunoglobulinlike cell adhesion molecule (IgCAM) domain ( Fig. 2A). MMP23 has been implicated in prostate, brain, and breast cancer (24 -26). In humans, two related sequences, MMP23A (a pseudogene) and MMP23B, are co-located on chromosome 1p36 (20). We have investigated MMP23 to gain insight into the structure and physiological functions of ShKT toxin domains and describe the solution structure of the MMP23 TxD domain, its * This work was supported, in whole or in part, by National Institutes of Health

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Molecular Evolution of Snake Toxins: Is the Functional Diversify of Snake Toxins Associated with a Mechanism of Accelerated Evolution?

Cited by 195 publications

References 185 publications

Snake Venomics of the Lancehead Pitviper Bothrops asper: Geographic, Individual, and Ontogenetic Variations

Snake Venomics of the Lancehead Pitviper Bothrops asper: Geographic, Individual, and Ontogenetic Variations

Phospholipases A₂ from Callosellasma rhodostoma venom gland

Potassium Channel Modulation by a Toxin Domain in Matrix Metalloprotease 23

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Molecular Evolution of Snake Toxins: Is the Functional Diversify of Snake Toxins Associated with a Mechanism of Accelerated Evolution?

Cited by 195 publications

References 185 publications

Snake Venomics of the Lancehead Pitviper Bothrops asper: Geographic, Individual, and Ontogenetic Variations

Snake Venomics of the Lancehead Pitviper Bothrops asper: Geographic, Individual, and Ontogenetic Variations

Phospholipases A2 from Callosellasma rhodostoma venom gland

Potassium Channel Modulation by a Toxin Domain in Matrix Metalloprotease 23

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Phospholipases A₂ from Callosellasma rhodostoma venom gland