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1fm6
From Proteopedia
THE 2.1 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF THE HETERODIMER OF THE HUMAN RXRALPHA AND PPARGAMMA LIGAND BINDING DOMAINS RESPECTIVELY BOUND WITH 9-CIS RETINOIC ACID AND ROSIGLITAZONE AND CO-ACTIVATOR PEPTIDES.
The nuclear receptor PPARgamma/RXRalpha heterodimer regulates glucose and lipid homeostasis and is the target for the antidiabetic drugs GI262570 and the thiazolidinediones (TZDs). We report the crystal structures of the PPARgamma and RXRalpha LBDs complexed to the RXR ligand 9-cis-retinoic acid (9cRA), the PPARgamma agonist rosiglitazone or GI262570, and coactivator peptides. The PPARgamma/RXRalpha heterodimer is asymmetric, with each LBD deviated approximately 10 degrees from the C2 symmetry, allowing the PPARgamma AF-2 helix to interact with helices 7 and 10 of RXRalpha. The heterodimer interface is composed of conserved motifs in PPARgamma and RXRalpha that form a coiled coil along helix 10 with additional charge interactions from helices 7 and 9. The structures provide a molecular understanding of the ability of RXR to heterodimerize with many nuclear receptors and of the permissive activation of the PPARgamma/RXRbeta heterodimer by 9cRA.
Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors., Gampe RT Jr, Montana VG, Lambert MH, Miller AB, Bledsoe RK, Milburn MV, Kliewer SA, Willson TM, Xu HE, Mol Cell. 2000 Mar;5(3):545-55. PMID:10882139
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1FM6 is a 8 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
See PPAR for additional structural information.
Reference
- Gampe RT Jr, Montana VG, Lambert MH, Miller AB, Bledsoe RK, Milburn MV, Kliewer SA, Willson TM, Xu HE. Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors. Mol Cell. 2000 Mar;5(3):545-55. PMID:10882139
Page seeded by OCA on Mon Feb 16 11:04:17 2009
Categories: Homo sapiens | Bledsoe, R K. | Jr., R T.Gampe. | Kliewer, S A. | Lambert, M H. | Milburn, M V. | Miller, A B. | Montana, V G. | Willson, T M. | Xu, H E. | The heterodimer of the nuclear receptor ligand binding domains of rxralpha and ppargamma bound respectively with 9-cis retinoic acid and rosiglitazone and co-activator peptide
