Browning Christopher, McEwen Alastair G, Mori Kotaro, Yokoi Taiyo, Moras Dino, Nakagawa Yoshiaki, Billas Isabelle M L
Centre for Integrative Biology (CBI), Department of Integrated Structural Biology, IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Illkirch, France.
Centre National de la Recherche Scientifique (CNRS), UMR 7104, Illkirch, France.
J Pestic Sci. 2021 Feb 20;46(1):88-100. doi: 10.1584/jpestics.D20-095.
The ecdysone receptor (EcR) possesses the remarkable capacity to adapt structurally to different types of ligands. EcR binds ecdysteroids, including 20-hydroxyecdysone (20E), as well as nonsteroidal synthetic agonists such as insecticidal dibenzoylhydrazines (DBHs). Here, we report the crystal structures of the ligand-binding domains of EcR/USP bound to the DBH agonist BYI09181 and to the imidazole-type compound BYI08346. The region delineated by helices H7 and H10 opens up to tightly fit a phenyl ring of the ligands to an extent that depends on the bulkiness of ring substituent. In the structure of 20E-bound EcR, this part of the ligand-binding pocket (LBP) contains a channel filled by water molecules that form an intricate hydrogen bond network between 20E and LBP. The water channel present in the nuclear receptor bound to its natural hormone acts as a critical molecular adaptation spring used to accommodate synthetic agonists inside its binding cavity.
蜕皮激素受体（EcR）具有在结构上适应不同类型配体的非凡能力。EcR能结合蜕皮类固醇，包括20-羟基蜕皮酮（20E），以及非甾体类合成激动剂，如杀虫双苯甲酰肼（DBH）。在此，我们报告了与DBH激动剂BYI09181和咪唑型化合物BYI08346结合的EcR/USP配体结合域的晶体结构。由螺旋H7和H10划定的区域会打开，以紧密容纳配体的苯环，其程度取决于环取代基的大小。在与20E结合的EcR结构中，配体结合口袋（LBP）的这一部分包含一个由水分子填充的通道，这些水分子在20E和LBP之间形成了一个复杂的氢键网络。与天然激素结合的核受体中存在的水通道，作为一个关键的分子适应弹簧，用于在其结合腔内容纳合成激动剂。
