人体生长激素及其受体的细胞外域:复杂的复杂的晶体结构
A M de Vos1, M Ultsch, A A Kossiakoff
1Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080.
概括
人体生长激素 (hGH) 以1:2的比例与它的受体结合,揭示出一个独特的四螺旋束结构. 这种相互作用是生长调节的关键,涉及信号转导的顺序受体二分化.
科学领域:
- 结构生物学 结构生物学
- 分子内分泌学分子内分泌学
- 生物化学 生物化学
背景情况:
- 人的正常生长和发育取决于人类生长激素 (hGH) 与其受体的结合.
- 了解hGH及其受体之间的分子相互作用对于破译生长调节途径至关重要.
研究的目的:
- 阐明人类生长激素 (hGH) 和其受体复合物的2.8安格斯特罗姆晶体结构.
- 描述hGH-hGHbp复合物的结合接口和结构特征.
主要方法:
- 在2.8安格斯特罗姆分辨率的X射线晶体学.
- 人体生长激素 (hGH) 与其受体 (hGHbp) 细胞外域之间的复合物的结构分析.
主要成果:
- 该复合体包括一个hGH分子与两个受体分子 (hGHbp) 结合.
- hGH表现出一种不寻常的四螺旋束拓,而hGHbp拥有两个不同的,类似免疫球蛋白的域.
- 两个hGHbp域都对激素结合有贡献,尽管激素的结合部位不同,但保留的残留物与hGH相互作用.
- 受体的碳基终端域之间存在显著的接触面,这表明了一种序列二元化机制.
结论:
- 结构数据揭示了一种新的1:2胆量计和hGH受体复合体中详细的分子相互作用.
- 这些发现支持了一种序列性受体二分化模型,这对hGH介导的信号转导具有潜在的关键性.
- 这项研究为理解hGH在生长和发育中的作用提供了结构基础.
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