1FM9

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 GI262570 AND CO-ACTIVATOR PEPTIDES.

Summary for 1FM9

• Entry DOI: 10.2210/pdb1fm9/pdb
• Related: 1FM6
• Descriptor: RETINOIC ACID RECEPTOR RXR-ALPHA, PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA, STEROID RECEPTOR COACTIVATOR, ... (6 entities in total)
• Functional Keywords: the heterodimer of the nuclear receptor ligand binding domains of rxralpha and ppargamma bound respectively with 9-cis retinoic acid and gi262570 and co-activator peptides, transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : P19793 P37231
• Total number of polymer chains: 4
• Total formula weight: 64221.36

Authors

Gampe Jr., R.T.,Montana, V.G.,Lambert, M.H.,Miller, A.B.,Bledsoe, R.K.,Milburn, M.V.,Kliewer, S.A.,Willson, T.M.,Xu, H.E. (deposition date: 2000-08-16, release date: 2001-02-16, Last modification date: 2024-02-07)

Primary citation

Gampe Jr., R.T.,Montana, V.G.,Lambert, M.H.,Miller, A.B.,Bledsoe, R.K.,Milburn, M.V.,Kliewer, S.A.,Willson, T.M.,Xu, H.E.
Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors.
Mol.Cell, 5:545-555, 2000

PubMed Abstract: 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.

PubMed: 10882139
DOI: 10.1016/S1097-2765(00)80448-7

Experimental method

X-RAY DIFFRACTION (2.1 Å)