1PRG

LIGAND BINDING DOMAIN OF THE HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA

Summary for 1PRG

• Entry DOI: 10.2210/pdb1prg/pdb
• Descriptor: PROTEIN (PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA) (2 entities in total)
• Functional Keywords: thiazolidinedione, ligand-binding domain, nuclear receptor, apo, transcription factor, orphan receptor, gene regulation
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P37231
• Total number of polymer chains: 2
• Total formula weight: 61667.70

Authors

Nolte, R.T.,Wisely, G.B.,Milburn, M.V. (deposition date: 1998-07-02, release date: 2001-01-13, Last modification date: 2023-12-27)

Primary citation

Nolte, R.T.,Wisely, G.B.,Westin, S.,Cobb, J.E.,Lambert, M.H.,Kurokawa, R.,Rosenfeld, M.G.,Willson, T.M.,Glass, C.K.,Milburn, M.V.
Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma.
Nature, 395:137-143, 1998

PubMed Abstract: The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-dependent transcription factor that is important in adipocyte differentiation and glucose homeostasis and which depends on interactions with co-activators, including steroid receptor co-activating factor-1 (SRC-1). Here we present the X-ray crystal structure of the human apo-PPAR-gamma ligand-binding domain (LBD), at 2.2 A resolution; this structure reveals a large binding pocket, which may explain the diversity of ligands for PPAR-gamma. We also describe the ternary complex containing the PPAR-gamma LBD, the antidiabetic ligand rosiglitazone (BRL49653), and 88 amino acids of human SRC-1 at 2.3 A resolution. Glutamate and lysine residues that are highly conserved in LBDs of nuclear receptors form a 'charge clamp' that contacts backbone atoms of the LXXLL helices of SRC-1. These results, together with the observation that two consecutive LXXLL motifs of SRC-1 make identical contacts with both subunits of a PPAR-gamma homodimer, suggest a general mechanism for the assembly of nuclear receptors with co-activators.

PubMed: 9744270
DOI: 10.1038/25931

Experimental method

X-RAY DIFFRACTION (2.2 Å)