Department of Chemistry-Biology, University of Québec at Trois-Rivières, Trois-Rivières, Québec, Canada.
RNA. 2010 Oct;16(10):1968-79. doi: 10.1261/rna.1994310. Epub 2010 Aug 20.
Biogenic polyamines are found to modulate protein synthesis at different levels. This effect may be explained by the ability of polyamines to bind and influence the secondary structure of tRNA, mRNA, and rRNA. We report the interaction between tRNA and the three biogenic polyamines putrescine, spermidine, spermine, and cobalt(III)hexamine at physiological conditions, using FTIR spectroscopy, capillary electrophoresis, and molecular modeling. The results indicated that tRNA was stabilized at low biogenic polyamine concentration, as a consequence of polyamine interaction with the backbone phosphate group. The main tRNA reactive sites for biogenic polyamine at low concentration were guanine-N7/O6, uracil-O2/O4, adenine-N3, and 2'OH of the ribose. At high polyamine concentration, the interaction involves guanine-N7/O6, adenine-N7, uracil-O2 reactive sites, and the backbone phosphate group. The participation of the polycation primary amino group, in the interaction and the presence of the hydrophobic contact, are also shown. The binding affinity of biogenic polyamine to tRNA molecule was in the order of spermine > spermidine > putrescine with K(Spm) = 8.7 × 10(5) M(-1), K(Spd) = 6.1 × 10(5) M(-1), and K(Put) = 1.0 × 10(5) M(-1), which correlates with their positively charged amino group content. Hill analysis showed positive cooperativity for the biogenic polyamines and negative cooperativity for cobalt-hexamine. Cobalt(III)hexamine contains high- and low-affinity sites in tRNA with K(1) = 3.2 × 10(5) M(-1) and K(2) = 1.7 × 10(5) M(-1), that have been attributed to the interactions with guanine-N7 sites and the backbone PO(2) group, respectively. This mechanism of tRNA binding could explain the condensation phenomenon observed at high Co(III) content, as previously shown in the Co(III)-DNA complexes.
生物源多胺被发现可在不同水平上调节蛋白质合成。这种效应可以通过多胺结合并影响 tRNA、mRNA 和 rRNA 的二级结构来解释。我们报告了在生理条件下 tRNA 与三种生物源多胺腐胺、亚精胺、精胺和钴(III)六胺之间的相互作用,使用傅里叶变换红外光谱、毛细管电泳和分子建模。结果表明,在低生物源多胺浓度下,tRNA 稳定存在,这是多胺与磷酸基团骨架相互作用的结果。在低浓度时,生物源多胺与 tRNA 反应的主要部位是鸟嘌呤-N7/O6、尿嘧啶-O2/O4、腺嘌呤-N3 和核糖的 2'OH。在高多胺浓度下,相互作用涉及鸟嘌呤-N7/O6、腺嘌呤-N7、尿嘧啶-O2 反应部位和磷酸基团骨架。还表明了多阳离子的伯氨基基团参与相互作用和存在疏水性接触。生物源多胺与 tRNA 分子的结合亲和力顺序为精胺>亚精胺>腐胺,K(Spm)=8.7×10(5)M(-1),K(Spd)=6.1×10(5)M(-1),K(Put)=1.0×10(5)M(-1),这与它们带正电荷的氨基含量有关。希夫分析表明,生物源多胺具有正协同性,而钴-六胺具有负协同性。钴(III)六胺在 tRNA 中含有高亲和性和低亲和性结合位点,K(1)=3.2×10(5)M(-1)和 K(2)=1.7×10(5)M(-1),分别归因于与鸟嘌呤-N7 部位和磷酸基团 PO(2)的相互作用。这种 tRNA 结合机制可以解释在高 Co(III)含量下观察到的凝聚现象,如先前在 Co(III)-DNA 复合物中所示。