通过负选择优化细胞蛋白相互作用网络中的特异性
Ali Zarrinpar1, Sang-Hyun Park, Wendell A Lim
1Program in Biological Sciences, University of California, San Francisco, 600 16th Street, San Francisco, California 94143-2240, USA.
Nature
|December 12, 2003
概括
酵母蛋白在细胞信号传递中表现出高度的特异性. Pbs2联体与Sho1 SH3域具有独特的相互作用,在生物网络中表现出最佳的特异性.
科学领域:
- 分子生物学分子生物学
- 系统生物学 系统生物学
- 进化生物学 进化生物学
背景情况:
- 细胞信号网络依赖于模块化蛋白相互作用域.
- 有机体拥有这些域的多个版本,如酵母中的27个Src同质性3 (SH3) 域.
- 由于域冗余,存在交叉反应的可能性.
研究的目的:
- 为了研究孤立的蛋白质相互作用域的特异性.
- 确定环境是否是信号网络特异性的唯一决定因素.
- 探索域-连接体相互作用的进化优化.
主要方法:
- 在体内和体外测试以测试Pbs2-SH3域相互作用.
- 分析与其他酵母SH3域的交叉活性.
- 在变异特异性的Pbs2动机变体中评估适应性缺陷.
主要成果:
- 在酵母蛋白质组中,Pbs2联体对酵母蛋白质组中的Sho1 SH3域具有近乎绝对的特异性.
- 没有观察到与其他酵母SH3域的交叉反应.
- 非酵母SH3域与Pbs2的特异性降低,变体导致适应性缺陷.
结论:
- 孤立的域-联体对可以实现高的生物特异性.
- Pbs2动机似乎被优化,以避免与酵母特异性SH3域的交叉反应.
- 整个系统的负选择驱动了复杂交互网络中的特异性优化.
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