The HIN domain of IFI-200 proteins consists of two OB folds

The HIN domain of IFI-200 proteins consists of two OB folds
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DOI:
10.1016/j.bbrc.2004.12.056
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发表时间:
2005-02-18
影响因子:
3.1
通讯作者:
Lengauer, T
Lengauer, T
中科院分区:
生物学4区
文献类型:
--
作者:
Albrecht, M;Choubey, D;Lengauer, T

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干扰素诱导型 p200 (IFI-200/HIN-200) 蛋白家族可调节细胞生长和分化,并赋予对肿瘤和病毒感染发展的抵抗力。 IFI-200 家族成员被认为是通过调节多种因子的转录活性以及通过 C 端 HIN 结构域与其他蛋白质相互作用来发挥其生物效应。然而,HIN 结构域的结构和功能仍然不清楚。因此,我们进行了全面的生物信息学分析,并组装了 IFI-200 蛋白基于结构的多序列比对。折叠识别方法的应用表明HIN结构域由两个连续的OB结构域组成。我们的 DNA 结合 HIN 结构域的结构模型为许多先前的实验观察结果提供了长期寻求的解释。我们的结果还提出了 IFI-200 蛋白作为转录调节剂以及作为参与免疫调节和细胞凋亡过程的蛋白的相互作用伙伴的尚未探索的功能作用的可能性。 (C) 2004 Elsevier Inc. 保留所有权利。
The interferon-inducible p200 (IFI-200/HIN-200) family of proteins regulates cell growth and differentiation, and confers resistance to the development of tumors and virus infections. IFI-200 family members are thought to exert their biological effects by modulation of the transcriptional activities of numerous factors and interaction with other proteins through the C-terminal HIN domains. However, the HIN domain structure and function have remained obscure. Therefore, we performed a comprehensive bio-informatics analysis and assembled a structure-based multiple sequence alignment of IFI-200 proteins. The application of fold recognition methods revealed that the HIN domain consists of two consecutive OB domains. Our structural models of DNA-binding HIN domains afford the long-sought interpretations for many previous experimental observations. Our results also raise the possibility of as yet unexplored functional roles of IFI-200 proteins as transcriptional regulators and as interaction partners of proteins involved in immunomodulatory and apoptotic processes. (C) 2004 Elsevier Inc. All rights reserved.