通过自动催化Asp-Pro裂纹进行VWD域稳定
Noa Yeshaya1, Prashant Kumar Gupta2, Orly Dym3
1Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
Protein science : a publication of the Protein Society
|February 21, 2024
概括
维莱布兰德因子D型 (VWD) 域的裂变,特别是FCGBP中的Asp-Pro区域,增强了对降解的抵抗力. 在VWD域中这种结构性可塑性可能有助于它们在细胞外环境中的功能.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- ·维勒布兰德因子D型 (VWD) 域在细胞外蛋白中普遍存在.
- 许多VWD域包含一个Gly-Asp-Pro-His (GDPH) 主题,经过翻译后被切割.
- Fc IgG 结合蛋白 (FCGBP) 拥有 13 个 VWD 域,其中 11 个具有 GDPH 位点.
研究的目的:
- 在FCGBP VWD域内调查Asp-Pro裂变的结构和生物物理影响.
- 了解翻译后裂变如何影响蛋白质的稳定性和结构.
主要方法:
- 用X射线晶体学来确定FCGBP片段的结构.
- 生物物理分析以评估蛋白质分解性降解耐力.
- 对VWD领域进行比较结构分析.
主要成果:
- 内源性Asp-Pro裂变增加了对外源性蛋白解的抵抗力.
- 晶体结构揭示了分裂后的新链末端的三级相互作用.
- 在裂变上游的Gly-Asp键采用了cis配置.
- 在FCGBP VWD域结构中观察到一个全球组织差异.
结论:
- 在FCGBP VWD域中Asp-Pro裂变赋予了蛋白质分解电阻.
- 翻译后的裂变导致了地方和全球的结构变化.
- 由裂变影响的VWD域可塑性可能对细胞外功能至关重要.
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