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锌指-DNA识别:Zif268-DNA复合物在2.1埃分辨率下的晶体结构

Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A.

作者信息

Pavletich N P, Pabo C O

机构信息

Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

出版信息

Science. 1991 May 10;252(5007):809-17. doi: 10.1126/science.2028256.

DOI:10.1126/science.2028256
PMID:2028256
Abstract

The zinc finger DNA-binding motif occurs in many proteins that regulate eukaryotic gene expression. The crystal structure of a complex containing the three zinc fingers from Zif268 (a mouse immediate early protein) and a consensus DNA-binding site has been determined at 2.1 angstroms resolution and refined to a crystallographic R factor of 18.2 percent. In this complex, the zinc fingers bind in the major groove of B-DNA and wrap part way around the double helix. Each finger has a similar relation to the DNA and makes its primary contacts in a three-base pair subsite. Residues from the amino-terminal portion of an alpha helix contact the bases, and most of the contracts are made with the guanine-rich strand of the DNA. This structure provides a framework for understanding how zinc fingers recognize DNA and suggests that this motif may provide a useful basis for the design of novel DNA-binding proteins.

摘要

锌指DNA结合基序存在于许多调节真核基因表达的蛋白质中。包含来自Zif268(一种小鼠即早蛋白)的三个锌指和一个共有DNA结合位点的复合物的晶体结构已在2.1埃分辨率下确定,并精修至晶体学R因子为18.2%。在该复合物中,锌指结合在B-DNA的大沟中,并部分环绕双螺旋。每个锌指与DNA具有相似的关系,并在一个三碱基对亚位点进行主要接触。α螺旋氨基末端部分的残基与碱基接触,且大多数接触是与DNA富含鸟嘌呤的链进行的。这种结构为理解锌指如何识别DNA提供了一个框架,并表明该基序可能为设计新型DNA结合蛋白提供有用的基础。

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