...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Thermodynamic signatures of the antigen binding site of mAb 447-52D targeting the third variable region of HIV-1 gp120
【24h】

Thermodynamic signatures of the antigen binding site of mAb 447-52D targeting the third variable region of HIV-1 gp120

机译：靶向HIV-1 gp120第三可变区的mAb 447-52D抗原结合位点的热力学特征

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The third variable region (V3) of HIV-1 gp120 plays a key role in viral entry into host cells; thus, it is a potential target for vaccine design. Human monoclonal antibody (mAb) 447-52D is one of the most broadly and potently neutralizing anti-V3 mAbs. We further characterized the 447-52D epitope by determining a high-resolution crystal structure of the Fab fragment in complex with a cyclic V3 and interrogated the antigen-antibody interaction by a combination of site-specific mutagenesis, isothermal titration calorimetry (ITC) and neutralization assays. We found that 447-52D's neutralization capability is correlated with its binding affinity and at 25 °C the Gibbs free binding energy is composed of a large enthalpic component and a small favorable entropic component. The large enthalpic contribution is due to (i) an extensive hydrogen bond network, (ii) a π-cation sandwiching the V3 crown apex residue Arg ~(315), and (iii) a salt bridge between the 447-52D heavy chain residue Asp~(H95) and Arg~(315). Arg~(315) is often harbored by clade B viruses; thus, our data explained why 447-52D preferentially neutralizes clade B viruses. Interrogation of the thermodynamic signatures of residues at the antigen binding interface gives key insights into their contributions in the antigen-antibody interaction.
机译：HIV-1 gp120的第三个可变区（V3）在病毒进入宿主细胞中起关键作用。因此，它是疫苗设计的潜在目标。人单克隆抗体（mAb）447-52D是最广泛和最有效的中和性抗V3 mAb之一。我们通过确定与环状V3结合的Fab片段的高分辨率晶体结构，进一步表征了447-52D表位，并通过位点特异性诱变，等温滴定量热（ITC）和中和相结合来询问抗原-抗体相互作用分析。我们发现447-52D的中和能力与其结合亲和力相关，在25°C时，吉布斯自由结合能由大的焓组分和小的有利的熵组分组成。较大的焓贡献是由于（i）广泛的氢键网络，（ii）将V3冠状顶点残基Arg〜（315）夹在中间的π-阳离子和（iii）447-52D重链残基之间的盐桥Asp〜（H95）和Arg〜（315）。 Arg〜（315）经常被进化枝B病毒所掩盖。因此，我们的数据解释了为什么447-52D优先中和进化枝B病毒。在抗原结合界面处对残基的热力学签名的询问提供了对其在抗原-抗体相互作用中的贡献的关键见解。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号