血管细胞粘附分子-1的整合素结合片段的晶体结构,分辨率为1.8 A
E Y Jones1, K Harlos, M J Bottomley
1Laboratory of Molecular Biophysics, Oxford Centre for Molecular Sciences, UK.
Nature
|February 9, 1995
概括
血管细胞粘附分子-1 (VCAM-1) 与VLA-4整合素结合. 晶体结构显示VCAM-1的整合素结合基因暴露在域1中,这对细胞粘附至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 血管细胞粘附分子-1 (VCAM-1) 是一种细胞表面的糖蛋白,可以调解细胞间的粘附.
- VCAM-1属于免疫球蛋白超级家族,在炎症中发挥作用,并作为病原体的细胞受体.
- 在体内占主导地位的VCAM-1形式具有七个域的细胞外区域,在域1和域4中保留了整合素结合动机.
研究的目的:
- 为了确定VCAM-1的VLA-4结合片段的晶体结构.
- 阐明VLA-4与VCAM-1结合的结构基础.
- 为了确定整合素结合基因的特定形状和位置.
主要方法:
- 使用X射线晶体学来确定VCAM-1 (域1和2) 的VLA-4结合片段的结构.
- 对晶体结构的分析,以确定整合素结合基因及其构造.
- 在VCAM-1结构上绘制VLA-4结合部位的映射.
主要成果:
- 确定了VCAM-1的前两个域的晶体结构.
- 一个高度暴露的整合素结合基因 (Q38IDSPL) 在位于循环的N端区域的域1中被确定.
- VLA-4结合部位被映射到CFGβ表的面部,与此前免疫球蛋白超级家族相互作用的发现相一致.
结论:
- 在VCAM-1域1中暴露的整合素结合基因采用了独特的形状.
- 预计这种构造在整合素结合性免疫球蛋白超级家族分子中是常见的.
- 该研究提供了对VLA-4/VCAM-1相互作用的结构性见解,这与了解细胞粘附和炎症有关.
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