Structure of the DNA-binding region of lac repressor inferred from its homology with cro repressor.
Structure of the DNA-binding region of lac repressor inferred from its homology with cro repressor.
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从其与 cro 阻遏物的同源性推断出 lac 阻遏物的 DNA 结合区结构。
DOI：
10.1073/pnas.79.5.1428
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发表时间：
1982
影响因子：
11.1
通讯作者：
Takeda,Y
中科院分区：
文献类型：
--
作者：
Matthews,BW;Ohlendorf,DH;Anderson,WF;Takeda,Y
结果表明，大肠杆菌lac阻遏蛋白25个氨基端残基的氨基酸序列和DNA基因序列与5种DNA结合蛋白的序列同源：来自噬菌体lambda和噬菌体434的cro阻遏蛋白，来自噬菌体lambda的cI和cII蛋白，以及来自沙门氏菌噬菌体P22的阻遏蛋白。 lac 阻遏蛋白与其他蛋白质之间的同源区域与 cro 阻遏蛋白的主要 DNA 结合区域一致。特别是，lac阻遏物的残基Tyr-17到Gln-26对应于cro阻遏物的α螺旋Gln-27到Ala-36，我们假设其结合在DNA的大沟内并主要负责蛋白质对DNA操纵子区域的识别[Anderson, W. F., Ohlendorf, D. H., Takeda, Y. & Matthews, B. W. (1981) Nature （伦敦）290, 754--758]。通过与 cro 阻遏物类比，我们提出 lac 阻遏物的残基 17--26 是 α 螺旋，并且该螺旋和相邻亚基中的双重相关 α 螺旋结合在 lac 操纵子的连续主沟内，其呈右手 Watson-Crick B-DNA 构象。此外，通过与 cro 阻遏蛋白类比，我们认为 lac 阻遏蛋白的残基 Thr-5 到 Ala-13 形成第二个 α 螺旋，部分有助于 DNA 结合。所提出的 lac 阻遏蛋白 DNA 结合区域的结构与化学保护数据和基因实验一致，该实验确定了阻遏蛋白中参与或不参与 DNA 结合的许多残基的可能位置。
It is shown that the amino acid sequence and the DNA gene sequence of the 25 amino-terminal residues of the lac repressor protein of Escherichia coli are homologous with the sequences of five DNA-binding proteins: the cro repressor proteins from phage lambda and phage 434, the cI and cII proteins from phage lambda, and the repressor protein from Salmonella phage P22. The region of homology between lac repressor and the other proteins coincides with the principal DNA-binding region of cro repressor. In particular, residues Tyr-17 through Gln-26 of lac repressor correspond to the alpha-helix Gln-27 through Ala-36 of cro repressor, which we have postulated to bind within the major groove of the DNA and to be primarily responsible for the recognition of the DNA operator region by the protein [Anderson, W. F., Ohlendorf, D. H., Takeda, Y. & Matthews, B. W. (1981) Nature (London) 290, 754--758]. By analogy with cro repressor, we propose that residues 17--26 of lac repressor are alpha-helical and that this helix and a twofold-related alpha-helix in an adjacent subunit bind within successive major grooves of the lac operator, which is in a right-handed Watson--Crick B-DNA conformation. Also, by analogy with cro repressor, we suggest that residues Thr-5 through Ala-13 of lac repressor form a second alpha-helix and contribute, in part, to DNA binding. The proposed structure for the DNA-binding region of lac repressor is consistent with chemical protection data and with genetic experiments identifying the probable locations of a number of the residues of the repressor protein that either do or do not participate in DNA binding.