在PSD95 (DLG-4基因) 中三PDZ域的演变
Riya Nilkant1, Lisa Y Mesrop2, Samuel Lobo3
1Department of Molecular, Cell and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA 93106, USA.
Molecular biology and evolution
|December 17, 2025
概括
编码突触蛋白PSD-95的DLG4基因,起源于古代的动物. 它的PDZ域是从单个祖先域进化而来的,其中键对于PDZ3连接体相互作用至关重要.
科学领域:
- 进化生物学是进化的生物学.
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 像DLG4 (编码PSD-95) 这样的突触蛋白质有很古老的起源,早于动物.
- DLG4是一种MAGUK蛋白质,具有保存的域结构,包括PDZ域.
研究的目的:
- 追踪DLG4的三PDZ域的进化历史,追溯到它们的深远祖先起源.
- 研究PDZ3域及其连接体CRIPT的保守结合机制.
主要方法:
- 对DLG4三PDZ域的遗传学分析.
- 进化规模建模 (ESM2) 用于域保护.
- 用于结构和结合分析的AlphaFold2多元体.
主要成果:
- DLG4 的 PDZ 域系起源于 Filozoa 中的一个单一的祖先域.
- 跨越动物王国的边界,PDZ域的身份被保留.
- 克里普特是一种PDZ3连接体,在Filozoa中保存,键是保护结合的关键.
结论:
- DLG4 的 PDZ 域架构是古老的,并且高度保存.
- 键代表了PDZ3-连接体相互作用的基本创新,允许更广泛的蛋白质-蛋白质相互作用.
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