On the ancestral recruitment of metalloproteinases into the venom of snakes

Casewell, Nicholas R.

doi:10.1016/j.toxicon.2012.02.006

Cited by 56 publications

(50 citation statements)

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“…Following the divergence of vipers from the remaining caenophidians, extensive gene duplication, domain loss, and positive selection resulted in generation of the P-I and P-II classes of SVMP within the viperid lineage (6 -8). These two derived classes found in viper venoms lack either the cysteine-rich domain (P-II) or the cysteinerich and disintegrin domains (P-I) (8,9). The signal peptide and the propeptide domain are typically cleaved off before expression although the latter has been detected in venoms on occasion (9).…”

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confidence: 99%

Differential Evolution and Neofunctionalization of Snake Venom Metalloprotease Domains

Brust

Sunagar

Undheim

et al. 2013

Molecular & Cellular Proteomics

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Snake venom metalloproteases (SVMP) are composed of five domains: signal peptide, propeptide, metalloprotease, disintegrin, and cysteine-rich. Secreted toxins are typically combinatorial variations of the latter three domains. The SVMP-encoding genes of Psammophis mossambicus venom are unique in containing only the signal and propeptide domains. We show that the Psammophis SVMP propeptide evolves rapidly and is subject to a high degree of positive selection. Unlike Psammophis, some species of Echis express both the typical multidomain and the unusual monodomain (propeptide only) SVMP, with the result that a lower level of variation is exerted upon the latter. We showed that most mutations in the multidomain Echis SVMP occurred in the protease domain responsible for proteolytic and hemorrhagic activities. The cysteinerich and disintegrin-like domains, which are putatively responsible for making the P-III SVMPs more potent than the P-I and P-II forms, accumulate the remaining variation. Thus, the binding sites on the molecule's surface are evolving rapidly whereas the core remains relatively conserved. Bioassays conducted on two post-translationally cleaved novel proline-rich peptides from the P. mossambicus propeptide domain showed them to have been neofunctionalized for specific inhibition of mammalian a7 neuronal nicotinic acetylcholine receptors. We show that the proline rich postsynaptic specific neurotoxic peptides from Azemiops feae are the result of convergent evolution within the precursor region of the C-type na- Snake venom metalloproteases (SVMP)1 evolved from ADAM (A disintegrin and metalloprotease) proteins that were recruited into the venom of snakes near the base of the advanced snake (Caenophidia) radiation. They have been identified in the venoms of all lineages of advanced snakes (1-5). The ancestral SVMP (P-III) contains (in downstream order) five domains: signal ϩ propeptide ϩ metalloprotease ϩ disintegrin ϩ cysteine rich. Following the divergence of vipers from the remaining caenophidians, extensive gene duplication, domain loss, and positive selection resulted in generation of the P-I and P-II classes of SVMP within the viperid lineage (6 -8). These two derived classes found in viper venoms lack either the cysteine-rich domain (P-II) or the cysteinerich and disintegrin domains (P-I) (8, 9). The signal peptide and the propeptide domain are typically cleaved off before expression although the latter has been detected in venoms on occasion (9). SVMP are often the dominant venom component in the venom of viperid snakes, but are typically much less significant in the venom of other snake families (10 -15). The majority of SVMP principally exhibit hemorrhagic activity, although other functions, such as the activation of prothrombin and Factor X, fibrin(ogen)olysis, apoptosis and the inhibition of platelet aggregation, have also been reported (16). Although SVMP-induced hemorrhage is primarily dependent on the proteolytic activity of the metalloprotease domain, the potency of this activity is incr...

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confidence: 99%

Differential Evolution and Neofunctionalization of Snake Venom Metalloprotease Domains

Brust

Sunagar

Undheim

et al. 2013

Molecular & Cellular Proteomics

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“…SVMPs sequences were reckoned into five domains: signal peptide, propeptide, metalloproteinase, desintegrin and cyestinerich domains based on their domain organization. Some researchers reported same result (Brust et al, 2013;Casewell, 2012;Ryan et al, 2003). Signal peptides of all the sequences are highly conserved and they are nearly identical.…”

Section: Resultsmentioning

confidence: 67%

Identification of accelerated evolution in the metalloproteinase domain of snake venom metalloproteinase sequences (SVMPs) through comparative analysis

Islam¹,

Roly²,

Ruhullah³

et al. 2016

Afr. J. Biotechnol.

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Computational protein sequence analysis is one of the most important tools used for understanding the evolution of closely related proteins sequences including snake venom metalloproteinase sequences (SVMPs) which give valuable information regarding genetic variations. The fundamental objective of the present study is to screen the evolution distributed in metalloproteinase domain regions of protein sequences among different SVMPs in snake species which are involved in a range of pathological disorders such as arthritis, atherosclerosis, liver fibrosis, cardiovascular, cancer, liver and neurodegenerative disorders. In fact, SVMPS are responsible for hemorrhage and may also interfere with the hemostatic system. A comparative characterization of the metalloproteinase sequences has been carried out to analyze their multiple sequence alignment, phylogenic tree, homology, physicochemical, secondary structural and functional properties. DNAMAN software was used for multiple sequence alignment, phylogenic tree and homology and Expasy's Prot-param server was used for amino acid composition, physico-chemical and functional characterization of these SVMPs sequences. Studies of secondary structure of these SVMPs were carried out by computational program. Based on the observed patterns of occurrence of atypical features, we hypothesize that amino acids of metalloproteinase domain region (66.63% identity) of protein sequences are highly changeable; whereas, signal peptide region (93.98% identity) is the lowest changeable protein sequence and the remaining other three domains such as propeptide region (87.36% identity), desintegrin domain region (78.63% identity) and cysteine-rich domain region (75.70% identity) show moderate changeable protein sequence. SVMPs might be an accelerated evolution, which is a key player in causing diseases. From the data, it can be suggested that over -changed metalloproteinase domain regions in snake venom metalloproteinase might be responsible for the generation of functional variation of proteins expressed, which in turn may lead to different disorders in humans after snake bite. The results of this study would be an effective tool for the study of mutation, drugs resistance mechanisms and development of new drugs for different diseases.

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“…Despite recent progress made in determining the biochemical activities and in elucidating the primary amino acid sequences and crystal structures of cloned or purified venom metalloproteinases [6,7], there is scarce knowledge regarding the relationship between metalloproteinases' tertiary structure and their physiological function. Snake venom metalloproteinases (SVMPs) have evolved from an ancient mammalian ADAM gene [8][9][10]. Hence, SVMPs and ADAMs share a similar secondary structural organization [11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Molecular models of the Mojave rattlesnake (Crotalus scutulatus scutulatus) venom metalloproteinases reveal a structural basis for differences in hemorrhagic activities

Dagda

Gasanov²,

Zhang³

et al. 2014

J Biol Phys

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Rattlesnake venom can differ in composition and in metalloproteinase-associated activities. The molecular basis for this intra-species variation in Crotalus scutulatus scutulatus (Mojave rattlesnake) remains an enigma. To understand the molecular basis for intra-species variation of metalloproteinase-associated activities, we modeled the threedimensional structures of four metalloproteinases based on the amino acid sequence of four variations of the proteinase domain of the C. s. scutulatus metalloproteinase gene (GP1, GP2, GP3, and GP4). For comparative purposes, we modeled the atrolysin metalloproteinases of C. atrox as well. All molecular models shared the same topology. While the atrolysin metalloproteinase molecular models contained highly conserved substrate binding sites, the Mojave rattlesnake metalloproteinases showed higher structural divergence when superimposed onto each other. The highest structural divergence among the four C. s. scutulatus molecular models was located at the northern cleft wall and the S' 1 -pocket of the substrate binding site, molecular regions that modulate substrate selectivity. Molecular dynamics and field potential maps for each C. s. scutulatus metalloproteinase model demonstrated that the non-hemorrhagic metalloproteinases (GP2 and GP3) contain highly basic molecular and field potential surfaces while the hemorrhagic metalloproteinases GP1 and atrolysin C showed extensive acidic field potential maps and shallow but less dynamic active site pockets. Hence, differences in the spatial arrangement of the northern cleft wall, the S' 1 -pocket, and the physico-chemical environment surrounding the catalytic site contribute to differences in metalloproteinase activities in the Mojave rattlesnake. Our results provide a structural basis for variation of metalloproteinase-associated activities in the rattlesnake venom of the Mojave rattlesnake.

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On the ancestral recruitment of metalloproteinases into the venom of snakes

Cited by 56 publications

References 41 publications

Differential Evolution and Neofunctionalization of Snake Venom Metalloprotease Domains

Differential Evolution and Neofunctionalization of Snake Venom Metalloprotease Domains

Identification of accelerated evolution in the metalloproteinase domain of snake venom metalloproteinase sequences (SVMPs) through comparative analysis

Molecular models of the Mojave rattlesnake (Crotalus scutulatus scutulatus) venom metalloproteinases reveal a structural basis for differences in hemorrhagic activities

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