Ingraham Holly A, Redinbo Matthew R
Department of Physiology, 1550 4(th) Street, University of California, San Francisco, Box 2611, Mission Bay Campus, San Francisco, CA 94143-2611, USA.
Curr Opin Struct Biol. 2005 Dec;15(6):708-15. doi: 10.1016/j.sbi.2005.10.009. Epub 2005 Nov 2.
Of the large nuclear hormone receptor superfamily of proteins, orphan nuclear receptors have remained a mystery owing to their lack of identified ligands and their constitutive nature. Now, structures of several ligand-binding domains of orphan receptors have provided some surprising insights that were not anticipated from molecular studies. Therefore, most orphan nuclear receptors have now been 'adopted' and their regulation has been shown to range from true ligand-independence to highly promiscuous ligand-dependence. Former orphan receptors have been found to contain ligand-binding pockets that range in volume from vast (>1600A3) to non-existent and have been shown to generate surface AF2 motifs that range from being multifunctionally active to distinctly inactive. Insights from these new structures illustrate how powerful a structural biology approach can be when integrated with molecular and cellular physiology.
在蛋白质的大型核激素受体超家族中，孤儿核受体由于缺乏已确定的配体及其组成性质，一直是个谜。现在，几种孤儿受体的配体结合结构域的结构提供了一些令人惊讶的见解，这些见解是分子研究未曾预料到的。因此，大多数孤儿核受体现在已被“收养”，并且已表明它们的调节范围从真正的配体非依赖性到高度混杂的配体依赖性。已发现以前的孤儿受体含有体积从巨大（>1600ų）到不存在的配体结合口袋，并且已表明会产生从多功能活跃到明显不活跃的表面AF2基序。这些新结构的见解说明了结构生物学方法与分子和细胞生理学相结合时的强大作用。
