Effect of heterodimer partner RXR{alpha} on PPAR{gamma} activation function-2 helix in solution

Journal Article · Fri Jan 04 04:00:00 EST 2008 · Biochemical and Biophysical Research Communications

OSTI ID:21033038

Minghe, Chen; Stanley, Susan E ^[1]; Li, Ellen ^[1]

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1. Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110 (United States)

The structural mechanism of allosteric communication between retinoid X receptor (RXR) and its heterodimer partners remains controversial. As a first step towards addressing this question, we report a nuclear magnetic resonance (NMR) study on the GW1929-bound peroxisome proliferator-activated receptor gamma (PPAR{gamma}) ligand-binding domain (LBD) with and without the 9-cis-retinoic acid (9cRA)-bound RXR{alpha} LBD. Sequence-specific {sup 13}C{sup {alpha}}, {sup 13}C{sup {beta}}, and {sup 13}CO resonance assignments have been established for over 95% of the 275 residues in the PPAR{gamma} LBD monomer. The {sup 1}HN, {sup 15}N, and {sup 13}CO chemical shift perturbations induced by the RXR{alpha} LBD binding are located at not only the heterodimer interface that includes the C-terminal residue Y477 but also residues Y473 and K474 in the activation function-2 (AF-2) helix. This result suggests that 9cRA-bound RXR{alpha} can affect the PPAR{gamma} AF-2 helix in solution and demonstrates that NMR is a powerful new tool for studying the mechanism of allosteric ligand activation in RXR heterodimers.

• OSTI ID: 21033038
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 365; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CHEMICAL SHIFT
LIGANDS
MONOMERS
NUCLEAR MAGNETIC RESONANCE
PERTURBATION THEORY
RECEPTORS
RETINOIC ACID