| Recombinant expression of mutants of the Frankenstein disintegrin, RTS-ocellatusin. Evidence for the independent origin of RGD and KTS/RTS disintegrins | |
| Sanz-Soler R1; Lorente C1; Company B1; Sanz L1; Juarez P1; Perez A1; Zhang Y2; Jin Y2; Chen RQ3; Eble JA4; Calvete JJ*1; Bolas G*1; jcalvete@ibv.csic.es; gbolas@ibv.csic.es | |
| 2012 | |
| 发表期刊 | TOXICON
 |
| 卷号 | 60期号:4页码:665-675 |
| 合作性质 | 其它 |
| 摘要 | The requirements to transform a short disintegrin of the RGD clade into an RTS disintegrin, were investigated through the generation of recombinant mutants of ocellatusin in which the RGD tripeptide was substituted for RTS in different positions along the integrin-specificity loop. Any attempt to create an active integrin alpha(1)beta(1) inhibitory motif within the specificity loop of ocellatusin was unsuccessful. Replacing the whole RGD-loop of ocellatusin by the RTS-loop of jerdostatin was neither sufficient for confering alpha(1)beta(1) binding specificity to this ocellatusin-RTS Frankenstein(2) mutant. Factors other than the integrin-binding loop sequence per se are thus required to transform a disintegrin scaffold from the RGD clade into another scaffold from the RTS/KTS clade. Moreover, our results provide evidences, that the RTS/ICTS short disintegrins have potentially been recruited into the venom gland of Eurasian vipers independently from the canonical neofunctionalization pathway of the RGD disintegrins. PCR-amplifications of jerdostatin-like sequences from a number of taxa across reptiles, including snakes (Crotalinae, Viperinae, and Elapidae taxa) and lizards (Lacertidae and Iguanidae) clearly showed that genes coding for RTS/KTS disintegrins existed long before the split of Lacertidae and Iguania, thus predating the recruitment of the SVMP precursors of disintegrins, providing strong support for the view of an independent evolutionary history of the RTS/KTS and the RGD clades of short disintegrins. (c) 2012 Elsevier Ltd. All rights reserved. |
| 关键词 | Recombinant Rgd-disintegrin Ocellatusin Recombinant Rts/kts-disintegrin Jerdostatin Evolution Of Disintegrins |
| 资助者 | This work has been financed by grants BFU2010-17373 (from the Ministerio de Economía y Competitividad, Madrid, Spain), PROMETEO/2010/005 (from the Generalitat Valenciana, Valencia, Spain), and grant SFB815 project A6 from Deutsche Forschungsgemeinschaft (to J.A.E.). This work is part of the PhD theses of GB (recipient of a JAE- Predoctoral fellowship) and RS-S (FPI predoctoral fellows). ; This work has been financed by grants BFU2010-17373 (from the Ministerio de Economía y Competitividad, Madrid, Spain), PROMETEO/2010/005 (from the Generalitat Valenciana, Valencia, Spain), and grant SFB815 project A6 from Deutsche Forschungsgemeinschaft (to J.A.E.). This work is part of the PhD theses of GB (recipient of a JAE- Predoctoral fellowship) and RS-S (FPI predoctoral fellows). ; This work has been financed by grants BFU2010-17373 (from the Ministerio de Economía y Competitividad, Madrid, Spain), PROMETEO/2010/005 (from the Generalitat Valenciana, Valencia, Spain), and grant SFB815 project A6 from Deutsche Forschungsgemeinschaft (to J.A.E.). This work is part of the PhD theses of GB (recipient of a JAE- Predoctoral fellowship) and RS-S (FPI predoctoral fellows). ; This work has been financed by grants BFU2010-17373 (from the Ministerio de Economía y Competitividad, Madrid, Spain), PROMETEO/2010/005 (from the Generalitat Valenciana, Valencia, Spain), and grant SFB815 project A6 from Deutsche Forschungsgemeinschaft (to J.A.E.). This work is part of the PhD theses of GB (recipient of a JAE- Predoctoral fellowship) and RS-S (FPI predoctoral fellows). |
| 收录类别 | SCI |
| 语种 | 英语 |
| 资助者 | This work has been financed by grants BFU2010-17373 (from the Ministerio de Economía y Competitividad, Madrid, Spain), PROMETEO/2010/005 (from the Generalitat Valenciana, Valencia, Spain), and grant SFB815 project A6 from Deutsche Forschungsgemeinschaft (to J.A.E.). This work is part of the PhD theses of GB (recipient of a JAE- Predoctoral fellowship) and RS-S (FPI predoctoral fellows). ; This work has been financed by grants BFU2010-17373 (from the Ministerio de Economía y Competitividad, Madrid, Spain), PROMETEO/2010/005 (from the Generalitat Valenciana, Valencia, Spain), and grant SFB815 project A6 from Deutsche Forschungsgemeinschaft (to J.A.E.). This work is part of the PhD theses of GB (recipient of a JAE- Predoctoral fellowship) and RS-S (FPI predoctoral fellows). ; This work has been financed by grants BFU2010-17373 (from the Ministerio de Economía y Competitividad, Madrid, Spain), PROMETEO/2010/005 (from the Generalitat Valenciana, Valencia, Spain), and grant SFB815 project A6 from Deutsche Forschungsgemeinschaft (to J.A.E.). This work is part of the PhD theses of GB (recipient of a JAE- Predoctoral fellowship) and RS-S (FPI predoctoral fellows). ; This work has been financed by grants BFU2010-17373 (from the Ministerio de Economía y Competitividad, Madrid, Spain), PROMETEO/2010/005 (from the Generalitat Valenciana, Valencia, Spain), and grant SFB815 project A6 from Deutsche Forschungsgemeinschaft (to J.A.E.). This work is part of the PhD theses of GB (recipient of a JAE- Predoctoral fellowship) and RS-S (FPI predoctoral fellows). |
| WOS记录号 | WOS:000306777100025 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/6999 |
| 专题 | 科研部门_生物毒素与人类疾病（张云） 科研部门_动物模型与人类重大疾病机理重点实验室 |
| 通讯作者 | jcalvete@ibv.csic.es; gbolas@ibv.csic.es |
| 作者单位 | 1.Instituto de Biomedicina de Valencia, C.S.I.C., Jaume Roig 11, 46010 Valencia, Spain 2.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China 3.La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA 4.Center for Molecular Medicine, Department of Vascular Matrix Biology, Frankfurt-am-Main, Germany |
| 推荐引用方式 GB/T 7714 | Sanz-Soler R,Lorente C,Company B,et al. Recombinant expression of mutants of the Frankenstein disintegrin, RTS-ocellatusin. Evidence for the independent origin of RGD and KTS/RTS disintegrins[J]. TOXICON,2012,60(4):665-675. |
| APA | Sanz-Soler R.,Lorente C.,Company B.,Sanz L.,Juarez P.,...&gbolas@ibv.csic.es.(2012).Recombinant expression of mutants of the Frankenstein disintegrin, RTS-ocellatusin. Evidence for the independent origin of RGD and KTS/RTS disintegrins.TOXICON,60(4),665-675. |
| MLA | Sanz-Soler R,et al."Recombinant expression of mutants of the Frankenstein disintegrin, RTS-ocellatusin. Evidence for the independent origin of RGD and KTS/RTS disintegrins".TOXICON 60.4(2012):665-675. |
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| 文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | ||
| 2012090401.pdf（1349KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | 请求全文 | |
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