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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Ligand-binding properties of a juvenile hormone receptor, Methoprene-tolerant
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Ligand-binding properties of a juvenile hormone receptor, Methoprene-tolerant

机译：甲氧戊丁耐受的幼体激素受体的配体结合特性

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摘要

Juvenile hormone (JH) is a sesquiterpenoid of vital importance for insect development, yet the molecular basis of JH signaling remains obscure, mainly because a bona fide JH receptor has not been identified. Mounting evidence points to the basic helix-loop-helix (bHLH)/Per-Arnt-Sim (PAS) domain protein Methoprene-tolerant (Met) as the best JH receptor candidate. However, details of how Met transduces the hormonal signal are missing. Here, we demonstrate that Met specifically binds JH III and its biologically active mimics, methoprene and pyriproxyfen, through its C-termi-nal PAS domain. Substitution of individual amino acids, predicted to form a ligand-binding pocket, with residues possessing bulkier side chains reduces JH III binding likely because of steric hindrance. Although a mutation that abolishes JH III binding does not affect a Met-Met complex that forms in the absence of methoprene, it prevents both the ligand-dependent dissociation of the Met-Met dimer and the ligand-dependent interaction of Met with its partner bHLH-PAS protein Taiman. These results show that Met can sense the JH signal through direct, specific binding, thus establishing a unique class of intracellular hormone receptors.
机译：少年激素（JH）是一种对昆虫发育至关重要的倍半萜，但是JH信号传导的分子基础仍然不清楚，主要是因为尚未发现真正的JH受体。越来越多的证据表明，基本的螺旋-环-螺旋（bHLH）/ Per-Arnt-Sim（PAS）域蛋白耐甲氧丁烯（Met）是最佳的JH受体候选物。但是，关于Met如何转导激素信号的细节尚不明确。在这里，我们证明了Met通过其C末端PAS结构域特异性结合JH III及其生物学活性模拟物甲氧戊二烯和吡ip氧基。预计将形成配体结合袋的单个氨基酸被具有较大侧链的残基取代，可能会由于空间位阻而降低JH III结合。尽管取消JH III结合的突变不会影响在没有甲氧戊二烯的情况下形成的Met-Met复合物，但它既阻止了Met-Met二聚体的配体依赖性解离，又阻止了Met及其伴侣bHLH的配体依赖性相互作用-PAS蛋白Taiman。这些结果表明，Met可以通过直接的特异性结合来感知JH信号，从而建立了独特的一类细胞内激素受体。

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    Jean-Philippe Charles; Thomas lwema; V. Chandana Epa; Keiko Takaki; Jan Rynes; Marek Jindra;

  • 作者单位

    Centre des Sciences du Gout et de I'Alimentation, Centre National de la Recherche Scientifique Unite Mixte de Recherche 6265, Institut National de la Recherche Agronomique Unite Mixte de Recherche 1324, Universite de Bourgogne, 21000 Dijon, France;

    Laboratoire de Cristallographie et Cristallogenese des Proteines, Institut de Biologie Structurale Jean-Pierre Ebel, Commissariat a l'Energie Atomique, Centre National de la Recherche Scientifique Unite Mixte de Recherche 5075, Universite Joseph Fourier Grenoble 1, 38027 Grenoble, France,Groupe de Recherche Immunopathologies et Maladies Infectieuses, University of La Reunion, Cyclotron Reunion Ocean Indien, 97491 Ste Clotilde, Reunion, France;

    Division of Materials Science and Engineering, Commonwealth Scientific and Industrial Research Organization, Parkville, Victoria 3052, Australia;

    Biology Center, Academy of Sciences of the Czech Republic, Ceske Budejovice 37005, Czech Republic;

    Department of Molecular Biology, University of South Bohemia, Ceske Budejovice 37005, Czech Republic;

    Biology Center, Academy of Sciences of the Czech Republic, Ceske Budejovice 37005, Czech Republic;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    structure modeling; insecticide action; metamorphosis; tribolium; drosophila;

    机译：结构建模;杀虫剂作用变态;bol虫果蝇;

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