RECOGNITION OF Z-RNA AND Z-DNA DETERMINANTS BY POLYAMINES IN SOLUTION - EXPERIMENTAL AND THEORETICAL-STUDIES
RECOGNITION OF Z-RNA AND Z-DNA DETERMINANTS BY POLYAMINES IN SOLUTION - EXPERIMENTAL AND THEORETICAL-STUDIES
复制标题
DOI：
10.1080/07391102.1988.10507714
复制
发表时间：
1988-10-01
影响因子：
4.4
通讯作者：
MARTON, LJ
中科院分区：
文献类型：
--
作者：
BASU, HS;FEUERSTEIN, BG;MARTON, LJ
质子化多胺是在某些多核苷酸中诱导左手Z型的最有效的阳离子之一。然而，尚不清楚这些阳离子是否与溶液中 Z 序列上的特定位点结合。我们通过测量多胺对纯化的免疫球蛋白 (IgG) 与 Z 螺旋不同区域结合的影响以及分子力学建模，研究了潜在的多胺结合位点。研究了抗 Z-DNA 和抗 Z-RNA IgG 与 Z 螺旋的特异性结合与亚精胺或精胺浓度的函数关系。对于对 Z 螺旋上的各种决定簇具有不同特异性的 IgG，多胺对抗体-核酸相互作用的影响是不同的。多胺抑制某些抗 Z IgG 的结合，这些抗 Z IgG 可能针对可能在主凸面和磷酸主链之间的界面处或附近的特定位点，最有可能是通过与抗体结合位点竞争。相比之下，多胺对针对由磷酸主链确定的位点的其他抗 Z IgG 没有影响。此外，这些阳离子可以增强抗 Z IgG 与螺旋主凸表面 C-5 位置的大基团的结合；这种增强可能与电荷中和有关。在这些条件下，没有观察到抗体与多胺的直接结合。这些数据表明溶液中的 Z-DNA 和 Z-RNA 上均存在多胺的特异性结合位点。这些结合位点与 Quigley 中在寡核苷酸晶体中观察到的结合位点有一些相似性（“分子结构和生物活性”，J.F.Griffin 和 W.L.Duax，编辑，Elsevier，Amsterdam（1982），第 317-331 页）。螺旋表面上特定精胺结合位点的实验证据得到了精胺与 (dG-dC)5 .cntdot 主沟相互作用的分子力学模型的支持。 Z-和B-形式的(dG-dC)5。 B 型和 Z 型含精胺寡核苷酸的晶体坐标被用作建模研究的起点。与Z型主凸面结合的精胺的势能远不如与B型主凹槽结合的精胺有利。然而，在钠离子存在的情况下，Z 型-精胺复合物比 B 型更受青睐。因此，理论和实验研究表明多胺可以特异性识别溶液和晶体中的 Z 螺旋决定簇。
Protonated polyamines are among the most efficient cations that induce the left-handed Z-form in certain polynucleotides. It is not known, however, whether these cations bind to specific sites on Z-sequences in solution. We have studied potential polyamine binding sites by measuring the effects of polyamines on the binding of purified immunoglobulins (IgGs) to different regions of the Z-helix and by molecular mechanics modeling. The specific binding of anti-Z-DNA and anti-Z-RNA IgGs to Z-helices was studied as a function of spermidine or spermine concentration. The effect of polyamines on the antibody-nucleic acid interaction was different for IgGs with different specificities for various determinants on the Z-helix. Polyamines inhibit the binding of certain anti-Z IgGs directed against specific sites probably at or near the interface between the major convex surface and the phosphate backbone, most likely by competing with the antibody binding site(s). In contrast, polyamines have no effect on other anti-Z IgGs directed against sites determined by the phosphate backbone. Furthermore, these cations can enhance the binding of anti-Z IgG directed against bulky groups at the C-5 position on the major convex surface of the helix; the enhancement may be related to charge neutralization. Under these conditions, no direct binding of antibodies with polyamines was observed. These data suggest the existence of a specific binding site(s) for polyamines on both Z-DNA and Z-RNA in solution. These binding sites have some similarity to those observed in oligonucleotide crystals in Quigley (in "Molecular Structure and Biological Activity", J.F. Griffin and W.L. Duax, eds., Elsevier, Amsterdam (1982), pp. 317-331). The experimental evidence for specific spermine binding sites on the helical surface was supported by molecular mechanics modeling of the interaction of spermine with the major groove of (dG-dC)5 .cntdot. (dG-dC)5 in both the Z- and B-forms. The crystal coordinates of spermine-containing oligonucleotides in both the B- and Z-forms were used as the starting points for modeling studies. The potential energy of spermine bound to the major convex surface of the Z-form was much less favorable than that of spermine bound to the major groove of the B-form. In the presence of sodium ions, however, the Z-form-spermine complexes were favored over the B-form. Thus, both theoretical and experimental studies indicate that polyamines can specifically recognize Z-helical determinants in solution as well as in crystals.