Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
BMC Evol Biol. 2010 Feb 12;10:40. doi: 10.1186/1471-2148-10-40.
The ecdysone receptor (EcR) regulates various cellular responses to ecdysteroids during insect development. Insects have multiple EcR isoforms with different N-terminal A/B domains that contain the isoform-specific activation function (AF)-1 region. Although distinct physiologic functions of the EcR isoforms have been characterized in higher holometabolous insects, they remain unclear in basal direct-developing insects, in which only A isoform has been identified. To examine the structural basis of the EcR isoform-specific AF-1 regions, we performed a comprehensive structural comparison of the isoform-specific region of the EcR-A and -B1 isoforms in insects.
The EcR isoforms were newly identified in 51 species of insects and non-insect arthropods, including direct-developing ametabolous and hemimetabolous insects. The comprehensive structural comparison revealed that the isoform-specific region of each EcR isoform contained evolutionally conserved microdomain structures and insect subgroup-specific structural modifications. The A isoform-specific region generally contained four conserved microdomains, including the SUMOylation motif and the nuclear localization signal, whereas the B1 isoform-specific region contained three conserved microdomains, including an acidic activator domain-like motif. In addition, the EcR-B1 isoform of holometabolous insects had a novel microdomain at the N-terminal end.
Given that the nuclear receptor AF-1 is involved in cofactor recruitment and transcriptional regulation, the microdomain structures identified in the isoform-specific A/B domains might function as signature motifs and/or as targets for cofactor proteins that play essential roles in the EcR isoform-specific AF-1 regions. Moreover, the novel microdomain in the isoform-specific region of the holometabolous insect EcR-B1 isoform suggests that the holometabolous insect EcR-B1 acquired additional transcriptional regulation mechanisms.
蜕皮激素受体（EcR）在昆虫发育过程中调节各种细胞对蜕皮激素的反应。昆虫具有多种 EcR 同工型，它们的 N 端 A/B 结构域包含同工型特异性激活功能（AF）-1 区域。尽管在高等完全变态昆虫中已经描述了 EcR 同工型的不同生理功能，但在仅鉴定出 A 同工型的基础直接发育的昆虫中，它们仍然不清楚。为了研究 EcR 同工型特异性 AF-1 区域的结构基础，我们对昆虫中 EcR-A 和-B1 同工型的同工型特异性区域进行了全面的结构比较。
在 51 种昆虫和非昆虫节肢动物中，包括直接发育的无变态和不全变态昆虫，新鉴定出了 EcR 同工型。全面的结构比较表明，每个 EcR 同工型的同工型特异性区域包含进化保守的微结构域结构和昆虫亚组特异性的结构修饰。A 同工型特异性区域通常包含四个保守的微结构域，包括 SUMOylation 基序和核定位信号，而 B1 同工型特异性区域包含三个保守的微结构域，包括酸性激活剂结构域样基序。此外，完全变态昆虫的 EcR-B1 同工型在 N 端具有新的微结构域。
鉴于核受体 AF-1 参与辅助因子的募集和转录调节，在同工型特异性 A/B 结构域中鉴定出的微结构域可能作为特征基序和/或作为辅助因子蛋白的靶标发挥作用，这些辅助因子蛋白在 EcR 同工型特异性 AF-1 区域中发挥重要作用。此外，完全变态昆虫 EcR-B1 同工型特异性区域的新微结构域表明，完全变态昆虫 EcR-B1 获得了额外的转录调节机制。
