CRINEPT-TROSY NMR reveals p53 core domain bound in an unfolded form to the chaperone Hsp90
CRINEPT-TROSY NMR reveals p53 core domain bound in an unfolded form to the chaperone Hsp90
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DOI：
10.1073/pnas.132393699
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发表时间：
2002-08-20
影响因子：
11.1
通讯作者：
Fersht, AR
中科院分区：
文献类型：
--
作者：
Rüdiger, S;Freund, SMV;Fersht, AR
分子伴侣 Hsp90 隔离具有不稳定核心结构域的肿瘤抑制因子 p53 的致癌突变体。目前尚不清楚 p53 是否以未折叠、部分折叠或扭曲的结构结合，正如 Hsp90 的任何结合底物的结构一样。详细分析其中一个组件（部分）展开的大型复合体的结构是一个特别困难的问题。我们通过横向弛豫优化核磁共振波谱结合互相关弛豫增强偏振转移 (CRINEPT-TROSY) 表明，与 Hsp90 结合在大约 200 kDa 复合物中的 p53 核心结构域主要是未折叠的，缺乏螺旋或片状二级结构。这种结合模式可能是 Hsp90 底物的一般特征。
The molecular chaperone Hsp90 sequesters oncogenic mutants of the tumor suppressor p53 that have unstable core domains. It is not known whether p53 is bound in an unfolded, partly folded, or distorted structure, as is unknown for the structure of any bound substrate of Hsp90. It is a particularly difficult problem to analyze in detail the structures of large complexes in which one component is (partly) unfolded. We have shown by transverse relaxation-optimized NMR spectroscopy combined with cross-correlated relaxation-enhanced polarization transfer (CRINEPT-TROSY) that p53 core domain bound in an approximate to200-kDa complex with Hsp90 was predominantly unfolded lacking helical or sheet secondary structure. This mode of binding might be a general feature of substrates of Hsp90.