Structural diversity and evolution of the N-terminal isoform-specific region of ecdysone receptor-A and -B1 isoforms in insects.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan. taka226@biol.s.u-tokyo.ac.jp
Takayuki
T
Watanabe
Hideaki
H
Takeuchi
Takeo
T
Kubo
D000595:Amino Acid Sequence; D000818:Animals; D001181:Arthropods / Q000235:genetics; D003001:Cloning, Molecular; D007313:Insecta / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D011987:Receptors, Steroid / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment
D020033:Protein Isoforms; D011987:Receptors, Steroid; C055469:ecdysone receptor