Doherty A J, Serpell L C, Ponting C P
Laboratory of Molecular Biophysics, University of Oxford, UK.
Nucleic Acids Res. 1996 Jul 1;24(13):2488-97. doi: 10.1093/nar/24.13.2488.
One, two or four copies of the 'helix-hairpin-helix' (HhH) DNA-binding motif are predicted to occur in 14 homologous families of proteins. The predicted DNA-binding function of this motif is shown to be consistent with the crystallographic structure of rat polymerase beta, complexed with DNA template-primer [Pelletier, H., Sawaya, M.R., Kumar, A., Wilson, S.H. and Kraut, J. (1994) Science 264, 1891-1903] and with biochemical data. Five crystal structures of predicted HhH motifs are currently known: two from rat pol beta and one each in endonuclease III, AlkA and the 5' nuclease domain of Taq pol I. These motifs are more structurally similar to each other than to any other structure in current databases, including helix-turn-helix motifs. The clustering of the five HhH structures separately from other bi-helical structures in searches indicates that all members of the 14 families of proteins described herein possess similar HhH structures. By analogy with the rat pol beta structure, it is suggested that each of these HhH motifs bind DNA in a non-sequence-specific manner, via the formation of hydrogen bonds between protein backbone nitrogens and DNA phosphate groups. This type of interaction contrasts with the sequence-specific interactions of other motifs, including helix-turn-helix structures. Additional evidence is provided that alphaherpesvirus virion host shutoff proteins are members of the polymerase I 5'-nuclease and FEN1-like endonuclease gene family, and that a novel HhH-containing DNA-binding domain occurs in the kinesin-like molecule nod, and in other proteins such as cnjB, emb-5 and SPT6.
据预测，“螺旋-发夹-螺旋”（HhH）DNA结合基序的一个、两个或四个拷贝存在于14个同源蛋白质家族中。该基序的预测DNA结合功能与大鼠聚合酶β与DNA模板-引物复合物的晶体结构[佩尔蒂埃，H.，萨亚，M.R.，库马尔，A.，威尔逊，S.H.和克劳特，J.（1994年）《科学》264卷，1891 - 1903页]以及生化数据一致。目前已知五个预测的HhH基序的晶体结构：两个来自大鼠pol β，内切核酸酶III、AlkA和Taq pol I的5'核酸酶结构域各有一个。这些基序彼此之间在结构上比当前数据库中的任何其他结构，包括螺旋-转角-螺旋基序，都更为相似。在搜索中，这五个HhH结构与其他双螺旋结构分开聚类，表明本文所述的14个蛋白质家族的所有成员都具有相似的HhH结构。通过与大鼠pol β结构类比，有人提出这些HhH基序中的每一个都通过蛋白质主链氮原子与DNA磷酸基团之间形成氢键，以非序列特异性方式结合DNA。这种相互作用类型与其他基序，包括螺旋-转角-螺旋结构的序列特异性相互作用形成对比。还提供了额外证据，证明α疱疹病毒病毒体宿主关闭蛋白是聚合酶I 5'-核酸酶和FEN1样内切核酸酶基因家族的成员，并且在类驱动蛋白分子nod以及其他蛋白质如cnjB、emb-5和SPT6中存在一个新的含HhH的DNA结合结构域。
