抗体CDR循环在结合时是否会改变形状?
Chu'nan Liu1, Lilian M Denzler1, Oliver E C Hood1
1Structural and Molecular Biology, Division of Biosciences, University College London, London, UK.
mAbs
|March 13, 2024
概括
抗体药物开发需要了解抗原结合. 这项研究分析了抗体结构,发现补充性决定区域 (CDR) 在结合时显示最小的构造变化,除了CDR-H3.
科学领域:
- 结构生物学是结构生物学.
- 免疫学 免疫学 免疫学
- 计算化学是一种计算化学.
背景情况:
- 抗体是关键的治疗药物,有100多种许可药物.
- 修改抗体亲和力需要了解抗体-抗原相互作用.
- 在抗原结合时,互补性决定区域 (CDR) 的形状变化仍然是一个悬而未决的问题.
研究的目的:
- 在抗体-抗原结合过程中进行CDR形状变化的大规模调查.
- 分析抗原结合对抗体CDR结构的影响.
- 为改善抗体建模和药物设计提供数据.
主要方法:
- 从蛋白质数据库中编制了177个抗体的数据集 (AbAgDb),这些抗体具有结合和不结合的结构.
- 使用RMSD分析分析了CDR中的Cα脊柱形状变化.
- 将绑定的CDR形态与未绑定的CDR的形态空间进行比较.
主要成果:
- 大多数CDR,除了CDR-H3,在抗原结合时表现出最小的形状变化.
- 70.6%和87%的CDR-H3s显示全球Cα RMSD≤1.0Å和≤2.0Å,分别.
- 大多数绑定的CDR构造在未绑定的CDR构造空间内被发现.
结论:
- 抗体CDRs,特别是CDR-H3,在结合抗原时经历了有限的形状调整.
- 现有的未结合的CDR形态数据足够地代表了大多数CDR的结合状态.
- 这些发现将为抗体建模,对接策略和药物开发提供信息.
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