THE X-RAY STRUCTURE OF A GROWTH-HORMONE PROLACTIN RECEPTOR COMPLEX
THE X-RAY STRUCTURE OF A GROWTH-HORMONE PROLACTIN RECEPTOR COMPLEX
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DOI：
10.1038/372478a0
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发表时间：
1994-12-01
期刊：
影响因子：
64.8
通讯作者：
KOSSIAKOFF, AA
中科院分区：
文献类型：
--
作者：
SOMERS, W;ULTSCH, M;KOSSIAKOFF, AA
人类垂体激素，生长激素（hGH）和催乳素（hPRL），调节各种生理过程，其中包括肌肉，骨和软骨细胞的生长和分化以及哺乳（1）。这些活动是由酶-受体结合启动的。hGH和hPRL受体（分别为hGH（R）和hPRL（R））是来自造血受体超家族1类的单程跨膜受体（2，3）。这种分类是基于其胞外结构域的序列相似性，特别是高度保守的五肽，所谓的“WSXWS盒”，其功能是有争议的。第1类中的所有配体通过簇集机制激活其各自的受体（4）。在hGH的情况下，激活涉及顺序过程中的受体同源二聚化：通过受体分子与中间体1：1复合物的结合形成含有一个配体和两个受体分子的活性三元复合物（5-8）。hPRL不与hGH受体结合，但hGH与hGH（R）和hPRL（R）结合，诱变研究表明hGH上的受体结合位点重叠（9）。我们在这里提出的晶体结构的1：1复合物的生长激素结合的细胞外结构域的hPRL（R）。与hGH-hGH（R）复合物（10）的比较揭示了hGH如何与两种明显不同的受体结合表面结合。
THE human pituitary hormones, growth hormone (hGH) and prolactin (hPRL), regulate a large variety of physiological processes, among which are growth and differentiation of muscle, bone and cartilage cells, and lactation(1). These activities are initiated by hormone-receptor binding. The hGH and hPRL receptors (hGH(R) and hPRL(R), respectively) are single-pass transmembrane receptors from class 1 of the haematopoietic receptor superfamily(2,3). This classification is based on sequence similarity in their extracellular domains, notably a highly conserved pentapeptide, the so-called 'WSXWS box', the function of which is controversial. All ligands in class 1 activate their respective receptors by clustering mechanisms(4). In the case of hGH, activation involves receptor homodimerization in a sequential process: the active ternary complex containing one ligand and two receptor molecules is formed by association of a receptor molecule to an intermediate 1:1 complex(5-8). hPRL does not bind to the hGH receptor, but hGH binds to both the hGH(R) and hPRL(R), and mutagenesis studies have shown that the receptor-binding sites on hGH overlap(9). We present here the crystal structure of the 1:1 complex of hGH bound to the extracellular domain of the hPRL(R). Comparisons with the hGH-hGH(R) complex(10) reveal how hGH can bind to the two distinctly different receptor binding surfaces.