对的抗体及其与2.8 A抗原复合物的晶体结构
R L Stanfield1, T M Fieser, R A Lerner
1Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, California 92037.
概括
对抗体 (Fab') 复合的结构分析与myohemerythrin抗原的复合揭示了采用β转变形态. 这种结构表明抗体与原生蛋白质的改变形式结合.
科学领域:
- 结构生物学是结构生物学.
- 免疫化学 免疫化学
- 蛋白质科学是一种蛋白质科学.
背景情况:
- 抗体对于免疫反应和诊断至关重要.
- 在分子水平上了解抗体-抗原相互作用是开发向疗法的关键.
- 肌红素 (Mhr) 是一种与氧结合的蛋白质,其结构和功能已得到充分研究.
研究的目的:
- 确定抗体片段 (Fab') 和其复合体与合成抗原的三维结构.
- 阐明抗体-的识别的结构基础.
- 为了比较其自由和结合状态中的抗体结构.
主要方法:
- 使用X射线晶体学以2.8A分辨率确定未结合的Fab'和Fab'-复合物的结构.
- 对于结构溶液,采用了分子替代方法.
- 分析了电子密度图,以解释形状和抗体结合部位.
主要成果:
- 抗体片段 (Fab') 和其复合体与19氨基酸肌体甲基的结构性特征.
- 抗原在抗体的结合口袋中采用了II型β转变形状,与其原生α螺旋结构不同.
- 结合界面揭示了互补的形状和显著的疏水性质,埋藏的表面积为460A2 () 和540A2 (抗体).
- 在结时,在抗体侧链和主链中观察到轻微但显著的重组.
结论:
- 确定的结构为单克隆抗体对类表位的分子识别提供了洞察力.
- 结合时的改变形状表明,抗体可能会向形状修饰或myohemerythrin的apo-forms.
- 结构发现与先前对表位和其细特异性的免疫学绘制相关.
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