ALTERNATING ZINC FINGERS IN THE HUMAN MALE-ASSOCIATED PROTEIN ZFY - HX3H AND HX4H MOTIFS ENCODE A LOCAL STRUCTURAL SWITCH
ALTERNATING ZINC FINGERS IN THE HUMAN MALE-ASSOCIATED PROTEIN ZFY - HX3H AND HX4H MOTIFS ENCODE A LOCAL STRUCTURAL SWITCH
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DOI：
10.1021/bi00103a002
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发表时间：
1991-10-01
期刊：
影响因子：
2.9
通讯作者：
WEISS, MA
中科院分区：
文献类型：
--
作者：
KOCHOYAN, M;KEUTMANN, HT;WEISS, MA
人类男性相关蛋白 ZFY 中的两指重复为经典和变异 Zn 指的比较 2D-NMR 研究提供了模型。 这种重复部分是由共有组氨酸 (HX3H) 和变体 (HX4H) 组氨酸间距之间的间隔交替定义的。 为了研究替代组氨酸间距之间“转换”的影响，我们设计了已知结构的代表性 HX4H 结构域的 HX3H 类似物 [ZFY-6; Kochoyan, M.、Havel, T.、Nguyen, D. T.、Dahl, C. E.、Keutmann, H. T. 和 Weiss, M. A. (1991) 生物化学 30, 3371-3386]。 HX3H 类似物（称为 ZFY-开关）形成四面体 Co2+ 复合物，其热力学稳定性与母体肽相似。 2D-NMR 研究表明，ZFY-switch 和 ZFY-6 虽然整体结构相似，但在缺失位点附近表现出显着的局部变化。 虽然天然指中的 HX4H 位点形成非标准环，但 ZFY 开关中的 HX3H 位点折叠为 C 端 α 螺旋的 3(10) 延伸，如在共有 HX3H 结构域的 NMR 溶液结构中观察到的那样 [Lee, M. S., Gippert, G. P., Soman, K. V., Case, D. A., & Wright, P. E. (1989) Science 245, 635-637] 以及代表性 Zn 指-DNA 复合物的晶体结构 [Pavletich, N. P., & Pabo, C. O. (1991) Science 252, 809-817]。 我们提出，不同的组氨酸间距（HX3H 和 HX4H）编码替代表面结构之间的局部转换，这对蛋白质-DNA 识别模型具有影响。
The two-finger repeat in the human male-associated protein ZFY provides a model for comparative 2D-NMR studies of classical and variant Zn fingers. This repeat is defined in part by an alternation in spacing between consensus (HX3H) and variant (HX4H) histidine spacings. To investigate the effects of a "switch" between alternative histidine spacings, we have designed an HX3H analogue of a representative HX4H domain of known structure [ZFY-6; Kochoyan, M., Havel, T., Nguyen, D. T., Dahl, C. E., Keutmann, H. T., & Weiss, M. A. (1991) Biochemistry 30, 3371-3386]. The HX3H analogue (designated ZFY-switch) forms a tetrahedral Co2+ complex whose thermodynamic stability is similar to that of the parent peptide. 2D-NMR studies demonstrate that ZFY-switch and ZFY-6, although similar in overall structure, exhibit significant local changes near the site of deletion. Whereas the HX4H site in the native finger forms a nonstandard loop, the HX3H site in ZFY-switch folds as a 3(10) extension of the C-terminal alpha-helix, as observed in the NMR solution structure of a consensus HX3H domain [Lee, M. S., Gippert, G. P., Soman, K. V., Case, D. A., & Wright, P. E. (1989) Science 245, 635-637] and in the crystal structure of a representative Zn finger-DNA complex [Pavletich, N. P., & Pabo, C. O. (1991) Science 252, 809-817]. We propose that variant histidine spacings (HX3H and HX4H) encode a local switch between alternative surface architectures with implications for models of protein-DNA recognition.