Hicks Joshua M, Hsu Victor L
Department of Biochemistry and Biophysics, Oregon State University, Corvallis 97331, USA.
Proteins. 2004 May 1;55(2):330-8. doi: 10.1002/prot.10630.
The poly-proline type II extended left-handed helical structure is well represented in proteins. In an effort to determine the helix's role in nucleic acid recognition and binding, a survey of 258 nucleic acid-binding protein structures from the Protein Data Bank was conducted. Results indicate that left-handed helices are commonly found at the nucleic acid interfacial regions. Three examples are used to illustrate the utility of this structural element as a recognition motif. The third K homology domain of NOVA-2, the Epstein-Barr nuclear antigen-1, and the Drosophila paired protein homeodomain all contain left-handed helices involved in nucleic acid interactions. In each structure, these helices were previously unidentified as left-handed helices by secondary structure algorithms but, rather, were identified as either having small amounts of hydrogen bond patterns to the rest of the protein or as being "unstructured." Proposed mechanisms for nucleic acid interactions by the extended left-handed helix include both nonspecific and specific recognition. The observed interactions indicate that this secondary structure utilizes an increase in protein backbone exposure for nucleic acid recognition. Both main-chain and side-chain atoms are involved in specific and nonspecific hydrogen bonding to nucleobases or sugar-phosphates, respectively. Our results emphasize the need to classify the left-handed helix as a viable nucleic acid recognition and binding motif, similar to previously identified motifs such as the helix-turn-helix, zinc fingers, leucine zippers, and others.
多聚脯氨酸II型延伸左旋螺旋结构在蛋白质中表现良好。为了确定该螺旋在核酸识别和结合中的作用，我们对蛋白质数据库中的258个核酸结合蛋白结构进行了调查。结果表明，左旋螺旋常见于核酸界面区域。我们用三个例子来说明这种结构元件作为识别基序的效用。NOVA - 2的第三个K同源结构域、爱泼斯坦 - 巴尔核抗原 - 1和果蝇配对蛋白同源结构域都含有参与核酸相互作用的左旋螺旋。在每个结构中，这些螺旋以前通过二级结构算法未被识别为左旋螺旋，而是被识别为与蛋白质其余部分具有少量氢键模式或被认为是“无结构的”。延伸左旋螺旋与核酸相互作用的推测机制包括非特异性和特异性识别。观察到的相互作用表明，这种二级结构利用增加的蛋白质主链暴露来进行核酸识别。主链和侧链原子分别参与与核碱基或糖 - 磷酸的特异性和非特异性氢键形成。我们的结果强调需要将左旋螺旋分类为一种可行的核酸识别和结合基序，类似于先前确定的基序，如螺旋 - 转角 - 螺旋、锌指、亮氨酸拉链等。
