基于结构的RNA结合锌指设计
Structure-based design of an RNA-binding zinc finger.
作者信息
McColl D J, Honchell C D, Frankel A D
机构信息
Department of Biochemistry and Biophysics, University of California, 513 Parnassus Avenue, San Francisco, CA 94143-0448, USA.
出版信息
Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9521-6. doi: 10.1073/pnas.96.17.9521.
Abstract
A structure-based approach was used to design RNA-binding zinc fingers that recognize the HIV-1 Rev response element (RRE). An arginine-rich alpha-helix from HIV-1 Rev was engineered into the zinc finger framework, and the designed fingers were shown to bind specifically to the RRE with high affinity and in a zinc-dependent manner, and display cobalt absorption and CD spectra characteristic of properly folded fingers. The results indicate that a monomeric zinc finger can recognize a specific nucleic acid site and that the alpha-helix of a finger can be used to recognize the major groove of RNA as well as DNA. The RRE-binding zinc fingers demonstrate how structure-based approaches may be used in the design of potential RNA-binding therapeutics and provide a framework for selecting RNA-binding fingers with desired specifications.
摘要
采用基于结构的方法设计了识别HIV-1 Rev反应元件（RRE）的RNA结合锌指。将来自HIV-1 Rev的富含精氨酸的α-螺旋构建到锌指框架中，结果表明设计的锌指能以锌依赖的方式，高亲和力地特异性结合RRE，并呈现出正确折叠的锌指所具有的钴吸收和圆二色光谱特征。结果表明，单体锌指能够识别特定的核酸位点，并且锌指的α-螺旋可用于识别RNA以及DNA的大沟。RRE结合锌指展示了基于结构的方法如何用于设计潜在的RNA结合治疗剂，并为选择具有所需特性的RNA结合锌指提供了一个框架。
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