在p21 ((WAF1/CIP1) 的C终端区域的结构与人类PCNA复杂
J M Gulbis1, Z Kelman, J Hurwitz
1Laboratory of Molecular Biophysics, The Rockefeller University, New York, New York 10021, USA.
Cell
|October 18, 1996
概括
晶体结构揭示了细胞循环蛋白p21 (WAF1/CIP1) 如何抑制DNA聚合酶三角流动性因子PCNA (增殖细胞核抗原). 这种相互作用涉及p21与PCNA形成β片,可能阻断其他聚合酶成分.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 增殖细胞核抗原 (PCNA) 是DNA聚合酶三角流动性的关键因素.
- 已知细胞循环检查点蛋白p21 (WAF1/CIP1) 抑制PCNA功能.
- 了解这种抑制的分子基础是理解细胞循环调节和DNA复制的关键.
研究的目的:
- 为了确定人类PCNA-p21复合体的高分辨率晶体结构.
- 为了阐明PCNA和p21之间的分子相互作用.
- 提供关于p21抑制PCNA活动的机制的见解.
主要方法:
- 使用X射线结晶学来确定结构.
- 该结构的分辨率为2.6安格斯特罗姆分辨率.
- 生物化学测试被用来确认相互作用和抑制机制.
主要成果:
- 成功确定了PCNA-p21复合物的晶体结构.
- p21以1:1的石化比率与PCNA结合.
- 一个显著的相互作用涉及p21与PCNA域间连接器循环形成β片,保持三元环结构.
- 在PCNA环内有一个中央孔仍然可用于DNA相互作用.
结论:
- 该p21广泛与PCNA结合,形成β片相互作用.
- 在p21结合时,PCNA的三元环结构被保留.
- p21可能通过硬质阻碍其他聚合酶组件组件的结合来抑制PCNA,而不是直接阻止DNA相互作用.
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