The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure.
The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure.
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DOI：
10.1016/s0021-9258(19)38926-4
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发表时间：
1990-05
期刊：
影响因子：
--
通讯作者：
R. Reeves;M. Nissen
中科院分区：
文献类型：
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作者：
R. Reeves;M. Nissen
我们已经确定了哺乳动物高迁移率组（HMG）I染色体蛋白的结构域，这些结构域对于与富含a.t的DNA片段的狭窄小槽结合是必要和充分的。每个已知的HMG-I蛋白中有三个高度保守的区域与共识序列T-P-K-R-P-R-G-R-P-K-K密切相关。与此一致的“结合域”（BD）序列相对应的合成寡肽以类似于完整的HMG-I蛋白的方式特异性地与底物DNA结合。分子coey - pauling - koltun模型的建立和使用能量最小化程序预测结构的计算机模拟表明，一致的BD肽具有类似于抗肿瘤和抗病毒药物netropsin和distamycin以及染料Hoechst 33258的二级结构。在体外实验中，这些配体也优先结合富含a.t的DNA，已被证明可以有效地与BD肽和HMG-I蛋白竞争DNA结合。BD肽还含有新的结构特征，如在其氨基末端预测的Asx弯曲或“钩”，以及横向突出的阳离子Arg/Lys侧链或“刷毛”，这可能有助于HMG-I蛋白的结合特性。预测的双肽结构，我们称之为“A.T钩”，代表了先前描述的dna结合基序，能够结合到A.T碱基对延伸的小凹槽上。
We have determined the domains of the mammalian high mobility group (HMG)I chromosomal proteins necessary and sufficient for binding to the narrow minor groove of stretches of A.T-rich DNA. Three highly conserved regions within each of the known HMG-I proteins is closely related to the consensus sequence T-P-K-R-P-R-G-R-P-K-K. A synthetic oligopeptide corresponding to this consensus "binding domain" (BD) sequence specifically binds to substrate DNA in a manner similar to the intact HMG-I proteins. Molecular Corey-Pauling-Koltun model building and computer simulations employing energy minimization programs to predict structure suggest that the consensus BD peptide has a secondary structure similar to the antitumor and antiviral drugs netropsin and distamycin and to the dye Hoechst 33258. In vitro these ligands, which also preferentially bind to A.T-rich DNA, have been demonstrated to effectively compete with both the BD peptide and the HMG-I proteins for DNA binding. The BD peptide also contains novel structural features such as a predicted Asx bend or "hook" at its amino-terminal end and laterally projecting cationic Arg/Lys side chains or "bristles" which may contribute to the binding properties of the HMG-I proteins. The predicted BD peptide structure, which we refer to as the "A.T-hook," represents a previously undescribed DNA-binding motif capable of binding to the minor groove of stretches of A.T base pairs.