PDBsum entry 1z5x

Hormone/growth factor receptor

PDB id: 1z5x

Contents

Protein chains

193 a.a. *

237 a.a. *

Ligands

PO4 ×4

P1A

* Residue conservation analysis

PDB id:

1z5x

Name:

Hormone/growth factor receptor

Title:

Hemipteran ecdysone receptor ligand-binding domain complexed with ponasterone a

Structure:

Ultraspiracle protein (usp) a homologue of rxr. Chain: u. Engineered: yes. Ecdysone receptor ligand binding domain. Chain: e. Fragment: ligand binding subunit. Engineered: yes

Source:

Bemisia tabaci. Organism_taxid: 7038. Gene: usp. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Gene: ecr.

Biol. unit:

Dimer (from PQS)

Resolution:

3.07Å R-factor: 0.205 R-free: 0.276

Authors:

J.A.Carmichael,M.C.Lawrence,L.D.Graham,P.A.Pilling,V.C.Epa,L.Noyce, G.Lovrecz,D.A.Winkler,A.Pawlak-Skrzecz

Key ref:

J.A.Carmichael et al. (2005). The X-ray structure of a hemipteran ecdysone receptor ligand-binding domain: comparison with a lepidopteran ecdysone receptor ligand-binding domain and implications for insecticide design. J Biol Chem, 280, 22258-22269. PubMed id: 15809296 DOI: 10.1074/jbc.M500661200

Date:

21-Mar-05 Release date: 05-Apr-05

Protein chain

No UniProt id for this chain

Struc: 193 a.a.

Protein chain

No UniProt id for this chain

Struc: 237 a.a.

DOI no: 10.1074/jbc.M500661200

J Biol Chem 280:22258-22269 (2005)

PubMed id: 15809296

The X-ray structure of a hemipteran ecdysone receptor ligand-binding domain: comparison with a lepidopteran ecdysone receptor ligand-binding domain and implications for insecticide design.

J.A.Carmichael, M.C.Lawrence, L.D.Graham, P.A.Pilling, V.C.Epa, L.Noyce, G.Lovrecz, D.A.Winkler, A.Pawlak-Skrzecz, R.E.Eaton, G.N.Hannan, R.J.Hill.

ABSTRACT

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.

Selected figure(s)

Figure 2.
FIG. 2. Schematic diagram of the structure of the B. tabaci ecdysone receptor LBD heterodimer showing the ecdysteroid-binding pocket. BtEcR-LBD is shown in yellow, and BtUSP-LBD is shown in cyan. Individual helices are shown as cylinders, and individual -strands are shown as arrows. The observed termini of each LBD are labeled. PonA is shown in green with oxygen atoms in red. Helices H3 and H12 of BtEcR-LBD are rendered transparent to enable viewing of the PonA moiety. The surface of the binding pocket is shown in transparent gray. The figure was produced using MOLSCRIPT (54), CONSCRIPT (55), and RASTER-3D (56).

Figure 3.
FIG. 3. Stereoviews of overlaid C^ backbone traces of the B. tabaci and H. virescens ecdysone receptor LBDs. a, BtEcR-LBD (black lines) and HvEcR-LBD (gray lines). The location of the ligand PonA is effectively identical in both LBD structures and is shown in ball-and-stick representation. b, BtUSP-LBD (black lines) and HvUSP-LBD (gray lines). Also shown is the location of the bound phospholipid in the HvUSP-LBD structure (ball-and-stick representation). The absence of helix H1 and the helix H1 to helix H3 connection is apparent in the BtUSP-LBD as well as the movement of the helix H6 to helix H7 loop and the helix H10 to helix H12 loop into the volume occupied by lipid in the HvUSP-LBD structure. The canonical -helices H1-H12 are labeled in both a and b as are the observed N and C termini. The figure was produced using MOLSCRIPT (54) and RASTER-3D (56).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 22258-22269) copyright 2005.

Figures were selected by an automated process.