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Updated: Jun 29, 2025

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对ZFAND1-p97相互作用的结构洞察力,涉及应力颗粒清除过程
Chih-Hsuan Lai1, Kuang-Ting Ko1, Pei-Ju Fan2
1Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
The Journal of biological chemistry
|March 27, 2024
概括
ZFAND1招募了p97来清除应力颗粒 (SG). 这项研究确定了ZFAND1域的原子结构,揭示了其泛胺类域 (UBL) 结合p97,影响p97.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 细胞应激反应的应激反应
背景情况:
- 化物暴露会诱导压力颗粒 (SG) 的形成,这是细胞对压力的反应.
- 在ATP依赖的解酶p97的帮助下,无素蛋白酶系统清除SGs.
- ZFAND1通过招募p97来促进SG清除,但其结构和相互作用机制尚不清楚.
研究的目的:
- 阐明ZFAND1和p97.7之间的相互作用的结构基础.
- 了解个别 ZFAND1 域在 p97 招聘和 SG 清除中的作用.
主要方法:
- 溶液态NMR光谱学和X射线晶体学用于确定ZFAND1域 (ZF1,ZF2,UBL) 的原子结构.
- 甲基NMR光谱和冷电子显微镜 (cryo-EM) 用于描述ZFAND1-p97相互作用.
- 15N旋转放松动态分析以评估域运动.
主要成果:
- 观察到ZFAND1.1的ZF1,ZF2和UBL的独立域运动.
- ZFAND1的UBL域,具有保存的β-抓取折叠和额外的N终端螺旋,与p97.7结合.
- 结合ZFAND1会在p97的N端域中诱导形状异质,影响其冷-EM密度.
结论:
- ZFAND1的C端UBL域对其与p97.7的相互作用至关重要.
- 结合ZFAND1调节p97的形状,提供了对SG清除机制的见解.
- 这项研究为了解p97-ZFAND1在细胞压力管理中的相互作用奠定了基础.
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