Epigallocatechin gallate, the main polyphenol in green tea, binds to the T-cell receptor, CD4: Potential for HIV-1 therapy
Epigallocatechin gallate, the main polyphenol in green tea, binds to the T-cell receptor, CD4: Potential for HIV-1 therapy
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DOI：
10.1016/j.jaci.2006.08.016
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发表时间：
2006-12-01
影响因子：
14.2
通讯作者：
Shearer, William T.
中科院分区：
文献类型：
--
作者：
Williamson, Mike P.;McCormick, Theron G.;Shearer, William T.
背景：绿茶黄酮表没食子儿茶素没食子酸酯(EGCG)被认为是通过阻止HIV-1糖蛋白(GP)120与T细胞上的CD4分子结合而发挥抗HIV-1作用的。目的：证实EGCG在gp120结合部位与CD4分子结合，并在生理水平上抑制gp120结合，从而为EGCG作为一种潜在的治疗HIV-1感染的药物奠定基础。方法：利用核磁共振波谱技术检测EGCG和对照(-)-儿茶素与CD4-Ig G(2)的结合。用流式细胞术分析gp120与人CD4(+)T细胞的结合。结果：在EGCG中加入CD4后，EGCG的核磁共振信号强度线性下降，而对照(-)-儿茶素的核磁共振信号强度没有线性下降。在饱和传递差实验中，加入5.8mU/L~310mU/L的EGCG，在EGCG的芳香环上产生了强烈的饱和，但相同浓度的(-)-儿茶素的影响要小得多，这意味着EGCG/CD_4的结合足够强，足以显著减少gp120/CD_4的结合。分子模拟研究表明，EGCG在CD4的D1域有一个结合位点，该区域是与gp120结合的口袋。生理相关浓度的没食子儿茶素没食子酸酯抑制gp120与分离的人CD_4(+)T细胞的结合。结论：我们已经证明了EGCG与CD_4分子的高亲和力结合的明显证据，K-d约为10nmol/L，并抑制了gp120与人CD_4(+)T细胞的结合。
Background: The green tea flavonoid, epigallocatechin gallate (EGCG), has been proposed to have an anti-HIV-1 effect by preventing the binding of HIV-1 glycoprotein (gp) 120 to the CD4 molecule on T cells.Objective: To demonstrate that EGCG binds to the CD4 molecule at the gp120 attachment site and inhibits gp120 binding at physiologically relevant levels, thus establishing EGCG as a potential therapeutic treatment for HIV-1 infection.Methods: Nuclear magnetic resonance spectroscopy was used to examine the binding of EGCG and control, (-)-catechin, to CD4-IgG(2) (PRO 542 (R)). Gp120 binding to human CD4(+) T cells was analyzed by flow cytometry.Results: Addition of CD4 to EGCG produced a linear decrease in nuclear magnetic resonance signal intensity from EGCG but not from the control, (-)-catechin. In saturation transfer difference experiments, addition of 5.8 mu mol/L CD4 to 310 mu mol/L EGCG produced strong saturation at the aromatic rings of EGCG, but identical concentrations of (-)-catechin produced much smaller effects, implying EGCG/CD4 binding strong enough to reduce gp120/CD4 binding substantially. Molecular modeling studies suggested a binding site for EGCG in the D1 domain of CD4, the pocket that binds gp120. Physiologically relevant concentrations of EGCG (0.2 mu mol/L) inhibited binding of gp120 to isolated human CD4(+) T cells.Conclusion: We have demonstrated clear evidence of high-affinity binding of EGCG to the CD4 molecule with a K-d of approximately 10 nmol/L and inhibition of gp120 binding to human CD4(+) T cells.Clinical implications: Epigallocatechin gallate has potential use as adjunctive therapy in HIV-1 infection.