通过蛋白质域扩展对PDZ域进行和能量重塑
Cristina Hidalgo-Carcedo1, Andre J Faure1,2, Aina Martí-Aranda3
1Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
Nature communications
|February 19, 2026
概括
蛋白质域扩展显著改变蛋白质能量格局,影响功能调节和进化. 这些变化为全性控制创造了新的可能性,影响了蛋白质稳定性和连接体结合.
科学领域:
- 蛋白质的结构和功能.
- 生物物理学的生物物理.
- 分子进化的分子进化.
背景情况:
- 蛋白质的功能是通过独立折叠的结构单元称为域.
- 域是保存的,但在蛋白质之间有所不同,影响调节和进化.
- 了解域扩展是蛋白质功能和适应性的关键.
研究的目的:
- 量化域扩展对蛋白质调节和可进化的能量影响.
- 研究结构化和动态扩展如何重塑蛋白质能量格局.
- 为了探索域修改的全性后果.
主要方法:
- 量化蛋白质变体丰富度和连接物结合超过19万种变体.
- 测量了PDZ域内的突变的自由能量变化.
- 评估了突变和两个域扩展之间的能量合.
主要成果:
- 结构和动态扩展都特别重塑了蛋白质能量格局.
- 删除一个α螺旋改变了50多个站点400多个突变的能量后果.
- 超过300个全基突变受到影响,包括那些溶剂可访问的部位.
结论:
- 域扩展或修剪修改了蛋白质的能量和性景观.
- 这些修改引入并消除了对蛋白质功能的全性控制的机会.
- 这为蛋白质进化和调节机制提供了洞察力.
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