Crystal structure of a heterodimeric complex of RAR and RXR ligand-binding domains
Crystal structure of a heterodimeric complex of RAR and RXR ligand-binding domains
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DOI：
10.1016/s1097-2765(00)80424-4
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发表时间：
2000-02-01
期刊：
影响因子：
16
通讯作者：
Moras, D
中科院分区：
文献类型：
--
作者：
Bourguet, W;Vivat, V;Moras, D
与选择性拮抗剂结合的人RAR α的配体结合结构域（LBD）和组成型活性小鼠RXR α F318 A突变体之间的异二聚体的晶体结构显示，通过配体的大体积延伸，RAR α螺旋H12采用拮抗剂位置。在RXR α F318 A的配体结合口袋中意外存在脂肪酸可能是其表观“组成性”的原因。“特定的构象变化表明了纯粹和部分拮抗作用的结构基础。RAR-RXR异二聚体界面与大多数核受体（NR）同源二聚体中观察到的界面相似。三维结构和序列的相关性分析提供了一个新的观点，核受体超家族成员之间的二聚体。
The crystal structure of a heterodimer between the ligand-binding domains (LBDs) of the human RAR alpha bound to a selective antagonist and the constitutively active mouse RXR alpha F318A mutant shows that, pushed by a bulky extension of the ligand, RAR alpha helix H12 adopts an antagonist position. The unexpected presence of a fatty acid in the ligand-binding pocket of RXR alpha F318A is likely to account for its apparent "constitutivity." Specific conformational changes suggest the structural basis of pure and partial antagonism. The RAR-RXR heterodimer interface is similar to that observed in most nuclear receptor (NR) homodimers. A correlative analysis of 3D structures and sequences provides a novel view on dimerization among members of the nuclear receptor superfamily.