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Scorpion Toxins: Positive Selection at a Distal Site Modulates Functional Evolution at a Bioactive Site
Zhu, Limei1; Gao, Bin; Yuan, Shouli; Zhu, Shunyi
2019
Source PublicationMOLECULAR BIOLOGY AND EVOLUTION
ISSN0737-4038
Volume36Issue:2Pages:365
AbstractThe bioactive sites of proteins are those that directly interact with their targets. In many immunity-and predation-related proteins, they frequently experience positive selection for dealing with the changes of their targets from competitors. However, some sites that are far away from the interface between proteins and their targets are also identified to evolve under positive selection. Here, we explore the evolutionary implication of such a site in scorpion a-type toxins affecting sodium (Na+) channels (abbreviated as alpha-ScNaTxs) using a combination of experimental and computational approaches. We found that despite no direct involvement in interaction with Na+ channels, mutations at this site by different types of amino acids led to toxicity change on both rats and insects in three a-ScNaTxs, accompanying differential effects on their structures. Molecular dynamics simulations indicated that the mutations changed the conformational dynamics of the positively selected bioactive site-containing functional regions by allosteric communication, suggesting a potential evolutionary correlation between these bioactive sites and the distant nonbioactive site. Our results reveal for the first time the cause of fast evolution at nonbioactive sites of scorpion neurotoxins, which is presumably to adapt to the change of their bioactive sites through coevolution to maintain an active conformation for channel binding. This might aid rational design of scorpion Na+ channel toxins with improved phyletic selectivity via modification of a distant nonbioactive site.
DepartmentLMB
Keywordbioactive site distal site toxin-channel interface long-range communication positive selection
DOI10.1093/molbev/msy223
Citation statistics
Document Type期刊论文
Identifierhttp://ir.scsio.ac.cn/handle/344004/17909
Collection中科院海洋生物资源可持续利用重点实验室
Affiliation1.Chinese Acad Sci, Grp Peptide Biol & Evolut, State Key Lab Integrated Management Pest Insects, Inst Zool, Beijing, Peoples R China
2.Chinese Acad Sci, South China Sea Inst Oceanol, Key Lab Trop Marine Bioresources & Ecol, Guangdong Prov Key Lab Appl Marine Biol, Guangzhou, Guangdong, Peoples R China
Recommended Citation
GB/T 7714
Zhu, Limei,Gao, Bin,Yuan, Shouli,et al. Scorpion Toxins: Positive Selection at a Distal Site Modulates Functional Evolution at a Bioactive Site[J]. MOLECULAR BIOLOGY AND EVOLUTION,2019,36(2):365, 375.
APA Zhu, Limei,Gao, Bin,Yuan, Shouli,&Zhu, Shunyi.(2019).Scorpion Toxins: Positive Selection at a Distal Site Modulates Functional Evolution at a Bioactive Site.MOLECULAR BIOLOGY AND EVOLUTION,36(2),365.
MLA Zhu, Limei,et al."Scorpion Toxins: Positive Selection at a Distal Site Modulates Functional Evolution at a Bioactive Site".MOLECULAR BIOLOGY AND EVOLUTION 36.2(2019):365.
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