Tan Xu, Calderon-Villalobos Luz Irina A, Sharon Michal, Zheng Changxue, Robinson Carol V, Estelle Mark, Zheng Ning
Department of Pharmacology, University of Washington, School of Medicine, Box 357280, Seattle, Washington 98195, USA.
Nature. 2007 Apr 5;446(7136):640-5. doi: 10.1038/nature05731.
Auxin is a pivotal plant hormone that controls many aspects of plant growth and development. Perceived by a small family of F-box proteins including transport inhibitor response 1 (TIR1), auxin regulates gene expression by promoting SCF ubiquitin-ligase-catalysed degradation of the Aux/IAA transcription repressors, but how the TIR1 F-box protein senses and becomes activated by auxin remains unclear. Here we present the crystal structures of the Arabidopsis TIR1-ASK1 complex, free and in complexes with three different auxin compounds and an Aux/IAA substrate peptide. These structures show that the leucine-rich repeat domain of TIR1 contains an unexpected inositol hexakisphosphate co-factor and recognizes auxin and the Aux/IAA polypeptide substrate through a single surface pocket. Anchored to the base of the TIR1 pocket, auxin binds to a partially promiscuous site, which can also accommodate various auxin analogues. Docked on top of auxin, the Aux/IAA substrate peptide occupies the rest of the TIR1 pocket and completely encloses the hormone-binding site. By filling in a hydrophobic cavity at the protein interface, auxin enhances the TIR1-substrate interactions by acting as a 'molecular glue'. Our results establish the first structural model of a plant hormone receptor.
生长素是一种关键的植物激素，它控制着植物生长和发育的许多方面。生长素由一小类F-box蛋白感知，包括运输抑制剂响应蛋白1（TIR1），它通过促进SCF泛素连接酶催化的Aux/IAA转录抑制因子的降解来调节基因表达，但TIR1 F-box蛋白如何感知生长素并被其激活仍不清楚。在这里，我们展示了拟南芥TIR1-ASK1复合物的晶体结构，该复合物处于游离状态以及与三种不同的生长素化合物和一种Aux/IAA底物肽形成的复合物状态。这些结构表明，TIR1富含亮氨酸的重复结构域含有一个意想不到的肌醇六磷酸辅助因子，并通过一个单一的表面口袋识别生长素和Aux/IAA多肽底物。生长素锚定在TIR1口袋的底部，与一个部分通用的位点结合，该位点也可以容纳各种生长素类似物。Aux/IAA底物肽对接在生长素的顶部，占据了TIR1口袋的其余部分，并完全包围了激素结合位点。通过填充蛋白质界面处的疏水腔，生长素作为一种“分子胶水”增强了TIR1与底物的相互作用。我们的结果建立了植物激素受体的第一个结构模型。
