Ecdysteroid receptors in imaginal discs of Drosophila melanogaster.

Yund, Mary Alice; King, David S.; Fristrom, James W.

doi:10.1073/pnas.75.12.6039

Cited by 106 publications

(38 citation statements)

References 22 publications

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“…Nevertheless the existing LBD structures do provide insight into the degree of substitution tolerated within the ecdysteroid ring system. For example the interaction between the 20-hydroxyl group of PonA and the hydroxyl group of the conserved residue HvEcR Tyr-408 (BtEcR Tyr-296) almost certainly underpins the well established higher activity of ecdysteroids possessing a 20-hydroxyl group, in particular the increased activity of the native hormone 20-hydroxyecdysone over ecdysone for dipteran and lepidopteran receptors (38). A similar hydrogen bond interaction between PonA and a tyrosine residue was observed in the corresponding HvEcR structure (16).…”

Section: Fig 5 Sequence Alignment Of the Lbds Of Btecr Hvecr Lxr␤mentioning

confidence: 71%

The X-ray Structure of a Hemipteran Ecdysone Receptor Ligand-binding Domain

Carmichael

Lawrence

Graham³

et al. 2005

Journal of Biological Chemistry

106

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The ecdysone receptor is a hormone-dependent transcription factor that plays a central role in regulating the expression of vast networks of genes during development and reproduction in the phylum Arthropoda. The functional receptor is a heterodimer of the two nuclear receptor proteins ecdysone receptor (EcR) and ultraspiracle protein. The receptor is the target of the environmentally friendly bisacylhydrazine insecticides, which are effective against Lepidoptera but not against Hemiptera or several other insect orders. Here we present evidence indicating that much of the selectivity of the bisacylhydrazine insecticides can be studied at the level of their binding to purified ecdysone receptor ligand-binding domain (LBD) heterodimers. We report the crystal structure of the ecdysone receptor LBD heterodimer of the hemipteran Bemisia tabaci (Bt, sweet potato whitefly) in complex with the ecdysone analogue ponasterone A. Although comparison with the corresponding known LBD structure from the lepidopteran Heliothis virescens (Hv) ecdysone receptor revealed the overall mode of ponasterone A binding to be very similar in the two cases, we observed that the BtEcR ecdysteroid-binding pocket is structured differently to that of HvEcR in those parts that are not in contact with ponasterone A. We suggest that these differences in the ligand-binding pocket may provide a molecular basis for the taxonomic order selectivity of bisacylhydrazine insecticides. The nuclear receptor (NR)1 family of proteins plays a crucial role in the regulation of transcription, and its members include the receptors for steroid hormones, vitamins, thyroid hormones, and bile acids (1). The human genome contains about 48 members of this family, and these have been studied extensively as therapeutic targets (2). The Arthropoda display a more limited suite of NRs (3) about 21 of which occur in Drosophila melanogaster. Among these is the receptor for the major arthropod steroid hormone, 20-hydroxyecdysone, which is involved in the regulation of insect molting, metamorphosis, and reproduction (4 -9). The receptor is absent from mammals and is thus potentially useful as a safe insecticide target. Indeed members of the bisacylhydrazine family exert their insecticidal activity by binding to the ecdysone receptor and exhibit remarkable taxonomic order selectivity (10, 11). These compounds act selectively on the Lepidoptera and certain Coleoptera (10) but are ineffective against insects of the hemipteran order and therefore cannot be used to control certain insect pests. A study (12) of two hemipteran insect predators (Geocoris punctipes and Orius insidiosus) showed that these beneficial (predatory) hemipterans are relatively insensitive to the bisacylhydrazine tebufenozide, whereas lepidopteran insect pests are susceptible. An improved understanding of variation in the structure of the ligand-binding pockets of ecdysone receptors and the basis of the specificity of these compounds at the atomic level of detail of their interaction with the receptor may aid ...

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Section: Fig 5 Sequence Alignment Of the Lbds Of Btecr Hvecr Lxr␤mentioning

confidence: 71%

The X-ray Structure of a Hemipteran Ecdysone Receptor Ligand-binding Domain

Carmichael

Lawrence

Graham³

et al. 2005

Journal of Biological Chemistry

106

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“…Thus, active ecdysones are known to bind with appropriate affinities to a nuclear protein (or proteins) present at low abundance in responsive cells and thought to be receptor(s) (Maroy et al 1978;Yund et al 1978;Sage et al 1982;Cherbas et al 1988), and a number of genes with the response characteristics of immediate hormone targets ("early effects") are known (for review, see Cherbas et al 1986a;Ashburner 1990;Segraves and Richards 1990). Using one of these genes (hsp27], Riddihough and Pelham (1987) described an upstream sequence sufficient to confer hormonal inducibility in transient assays.…”

mentioning

confidence: 99%

Identification of ecdysone response elements by analysis of the Drosophila Eip28/29 gene.

Cherbas¹,

Lee²,

Cherbas³

1991

Genes Dev.

221

114

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“…Accordingly, we could not detect any specific [3H]PoAbinding sites in 'cytosol' obtained from Calliphora larvae [9]. Other experimental systems, however, e. g. mass-isolated imaginal discs from Drosophila [29] or cultured Drosophila cells [27], have allowed the preparation of 'cytoplasmic' ecdysteroid receptors although the localization might represent an artifact of homogenization. These systems are possibly better suited to tackling the question of receptor activation.…”

Section: Discussionmentioning

confidence: 99%

Ecdysteroid receptors of the blowfly Calliphora vicina

Lehmann

Koolman

1989

European Journal of Biochemistry

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Ecdysteroids, the molting hormones of arthropods, act like vertebrate steroid hormones by binding to an intracellular receptor protein. We have recently isolated a protein from nuclei of blowfly larvae which has satisfied the requirements of an ecdysteroid receptor. The receptor was partially purified and its ecdysteroid-binding properties were characterized. The availability of receptor preparations which have been stabilized by partial purification now enables us to study the general DNA-binding properties of ecdysteroid receptors.DNA-binding characteristics of ecdysteroid receptors were studied with calf thymus DNA. Affinity for DNA was observed both in the presence and in the absence of steroid ligand but the ligand clearly enhanced binding of receptors to DNA. Receptor preparations contained a heterogeneous mixture of receptors; up to 25% of DNA-binding receptors, and nonbinding forms of ecdysteroid receptors. The ability to bind to DNA was subject to inactivation which was not affected by partial purification, but which could be decelerated by dilution of the receptor preparation. Thus, dilution resulted in a spurious activation of DNA binding. A genuine activation, which would have led to an increase in the percentage of the DNA-binding form of the ecdysteroid receptor complex, was not observed.

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Ecdysteroid receptors in imaginal discs of Drosophila melanogaster.

Abstract: ABSTRACT[3HJPonasterone A (PNA) of high specific activity has been used to identify and begin characterization of ecdysteroid (

Cited by 106 publications

References 22 publications

The X-ray Structure of a Hemipteran Ecdysone Receptor Ligand-binding Domain

The X-ray Structure of a Hemipteran Ecdysone Receptor Ligand-binding Domain

Identification of ecdysone response elements by analysis of the Drosophila Eip28/29 gene.

Ecdysteroid receptors of the blowfly Calliphora vicina

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