Rhodes D, Schwabe J W, Chapman L, Fairall L
MRC Laboratory of Molecular Biology, Cambridge, U.K.
Philos Trans R Soc Lond B Biol Sci. 1996 Apr 29;351(1339):501-9. doi: 10.1098/rstb.1996.0048.
Understanding how proteins recognize DNA in a sequence-specific manner is central to our understanding of the regulation of transcription and other cellular processes. In this article we review the principles of DNA recognition that have emerged from the large number of high-resolution crystal structures determined over the last 10 years. The DNA-binding domains of transcription factors exhibit surprisingly diverse protein architectures, yet all achieve a precise complementarity of shape facilitating specific chemical recognition of their particular DNA targets. Although general rules for recognition can be derived, the complex nature of the recognition mechanism precludes a simple recognition code. In particular, it has become evident that the structure and flexibility of DNA and contacts mediated by water molecules contribute to the recognition process. Nevertheless, based on known structures it has proven possible to design proteins with novel recognition specificities. Despite this considerable practical success, the thermodynamic and kinetic properties of protein/DNA recognition remain poorly understood.
了解蛋白质如何以序列特异性方式识别DNA是我们理解转录调控和其他细胞过程的核心。在本文中，我们回顾了过去10年中通过大量高分辨率晶体结构所揭示的DNA识别原理。转录因子的DNA结合结构域展现出惊人多样的蛋白质结构，但它们都实现了形状上的精确互补，从而促进对其特定DNA靶点的特异性化学识别。尽管可以推导出识别的一般规则，但识别机制的复杂性使得无法形成简单的识别密码。特别是，DNA的结构和灵活性以及水分子介导的相互作用对识别过程的贡献已变得显而易见。然而，基于已知结构，已证明有可能设计出具有新颖识别特异性的蛋白质。尽管取得了这一相当大的实际成功，但蛋白质/DNA识别的热力学和动力学性质仍知之甚少。
