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Target-Driven Evolution of Scorpion Toxins.

Zhang S, Gao B, Zhu S - Sci Rep (2015)

Bottom Line: By using maximum-likelihood models of codon substitution, we analyzed molecular adaptation in scorpion sodium channel toxins from a specific species and found ten positively selected sites, six of which are located at the core-domain of scorpion α-toxins, a region known to interact with two adjacent loops in the voltage-sensor domain (DIV) of sodium channels, as validated by our newly constructed computational model of toxin-channel complex.This work presents an example of atypical co-evolution between animal toxins and their molecular targets, in which toxins suffered from more prominent selective pressure from the channels of their competitors.Our discovery helps explain the evolutionary rationality of gene duplication of toxins in a specific venomous species.

View Article: PubMed Central - PubMed

Affiliation: Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects &Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, 100101 Beijing, China.

ABSTRACT
It is long known that peptide neurotoxins derived from a diversity of venomous animals evolve by positive selection following gene duplication, yet a force that drives their adaptive evolution remains a mystery. By using maximum-likelihood models of codon substitution, we analyzed molecular adaptation in scorpion sodium channel toxins from a specific species and found ten positively selected sites, six of which are located at the core-domain of scorpion α-toxins, a region known to interact with two adjacent loops in the voltage-sensor domain (DIV) of sodium channels, as validated by our newly constructed computational model of toxin-channel complex. Despite the lack of positive selection signals in these two loops, they accumulated extensive sequence variations by relaxed purifying selection in prey and predators of scorpions. The evolutionary variability in the toxin-bound regions of sodium channels indicates that accelerated substitutions in the multigene family of scorpion toxins is a consequence of dealing with the target diversity. This work presents an example of atypical co-evolution between animal toxins and their molecular targets, in which toxins suffered from more prominent selective pressure from the channels of their competitors. Our discovery helps explain the evolutionary rationality of gene duplication of toxins in a specific venomous species.

No MeSH data available.


Five top ZDOCK complexes between BmKM1 and the rNav1.2 VSD.These complexes are displayed in a tube style with WebLabViewer (MSI, San Diego, California, USA). Disulfide bond connectivities in BmKM1 (pdb entry 1SN1) are shown as sticks. The toxin has only 3.77 Å of root-mean-square deviation (RMSD) among different complexes, as calculated by Swiss-PdbViewer (http://spdbv.vital-it.ch/).
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f2: Five top ZDOCK complexes between BmKM1 and the rNav1.2 VSD.These complexes are displayed in a tube style with WebLabViewer (MSI, San Diego, California, USA). Disulfide bond connectivities in BmKM1 (pdb entry 1SN1) are shown as sticks. The toxin has only 3.77 Å of root-mean-square deviation (RMSD) among different complexes, as calculated by Swiss-PdbViewer (http://spdbv.vital-it.ch/).

Mentions: Previous experiments have indicated that two extracellular loops linking S1–S2 and S3–S4 in the domain IV VSD of Nav channels (LDIVS1-S2; LDIVS3-S4) are main regions of site 3 directly interacting with the core-domain of α-toxins2324. The pore module of domain I in Nav channels forms a secondary site by the interaction with the NC-domain of toxins2224252627. To observe the location of the PSSs in the interface of toxin-channel, we constructed a complex model between BmKM1, an extensively studied and structurally known M. martensii α-like toxin, and the DIV VSD of rNav1.2 using the ZDOCK server28. The channel structure used here is the one previously successfully used in exploring the binding mode of a scorpion α-toxin (AaHII)29. As shown in Fig. 2, in the five top ZDOCK models, BmKM1 similarly binds to the VSD (Fig. 2) and we thus selected the top 1 model for further analysis.


Target-Driven Evolution of Scorpion Toxins.

Zhang S, Gao B, Zhu S - Sci Rep (2015)

Five top ZDOCK complexes between BmKM1 and the rNav1.2 VSD.These complexes are displayed in a tube style with WebLabViewer (MSI, San Diego, California, USA). Disulfide bond connectivities in BmKM1 (pdb entry 1SN1) are shown as sticks. The toxin has only 3.77 Å of root-mean-square deviation (RMSD) among different complexes, as calculated by Swiss-PdbViewer (http://spdbv.vital-it.ch/).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4595728&req=5

f2: Five top ZDOCK complexes between BmKM1 and the rNav1.2 VSD.These complexes are displayed in a tube style with WebLabViewer (MSI, San Diego, California, USA). Disulfide bond connectivities in BmKM1 (pdb entry 1SN1) are shown as sticks. The toxin has only 3.77 Å of root-mean-square deviation (RMSD) among different complexes, as calculated by Swiss-PdbViewer (http://spdbv.vital-it.ch/).
Mentions: Previous experiments have indicated that two extracellular loops linking S1–S2 and S3–S4 in the domain IV VSD of Nav channels (LDIVS1-S2; LDIVS3-S4) are main regions of site 3 directly interacting with the core-domain of α-toxins2324. The pore module of domain I in Nav channels forms a secondary site by the interaction with the NC-domain of toxins2224252627. To observe the location of the PSSs in the interface of toxin-channel, we constructed a complex model between BmKM1, an extensively studied and structurally known M. martensii α-like toxin, and the DIV VSD of rNav1.2 using the ZDOCK server28. The channel structure used here is the one previously successfully used in exploring the binding mode of a scorpion α-toxin (AaHII)29. As shown in Fig. 2, in the five top ZDOCK models, BmKM1 similarly binds to the VSD (Fig. 2) and we thus selected the top 1 model for further analysis.

Bottom Line: By using maximum-likelihood models of codon substitution, we analyzed molecular adaptation in scorpion sodium channel toxins from a specific species and found ten positively selected sites, six of which are located at the core-domain of scorpion α-toxins, a region known to interact with two adjacent loops in the voltage-sensor domain (DIV) of sodium channels, as validated by our newly constructed computational model of toxin-channel complex.This work presents an example of atypical co-evolution between animal toxins and their molecular targets, in which toxins suffered from more prominent selective pressure from the channels of their competitors.Our discovery helps explain the evolutionary rationality of gene duplication of toxins in a specific venomous species.

View Article: PubMed Central - PubMed

Affiliation: Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects &Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, 100101 Beijing, China.

ABSTRACT
It is long known that peptide neurotoxins derived from a diversity of venomous animals evolve by positive selection following gene duplication, yet a force that drives their adaptive evolution remains a mystery. By using maximum-likelihood models of codon substitution, we analyzed molecular adaptation in scorpion sodium channel toxins from a specific species and found ten positively selected sites, six of which are located at the core-domain of scorpion α-toxins, a region known to interact with two adjacent loops in the voltage-sensor domain (DIV) of sodium channels, as validated by our newly constructed computational model of toxin-channel complex. Despite the lack of positive selection signals in these two loops, they accumulated extensive sequence variations by relaxed purifying selection in prey and predators of scorpions. The evolutionary variability in the toxin-bound regions of sodium channels indicates that accelerated substitutions in the multigene family of scorpion toxins is a consequence of dealing with the target diversity. This work presents an example of atypical co-evolution between animal toxins and their molecular targets, in which toxins suffered from more prominent selective pressure from the channels of their competitors. Our discovery helps explain the evolutionary rationality of gene duplication of toxins in a specific venomous species.

No MeSH data available.