RSS

PDB:2LBD

Protein Name

Retinoic acid receptor-gamma / retinoic acid complex

Species

Homo sapiens (human)

Biological Context

Retinoic acids (RAs) have important effects on many biological processes, including the regulation of cell growth, differentiation and apoptosis . RAs are used as preventive and therapeutic agents for a variety of human cancers. These effects of RAs are mediated by two classes of the retinoid receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). The RARs and RXRs belong to the nuclear receptor superfamily and are each made up of three receptor isotypes, called alpha, beta and gamma. These receptors are ligand-inducible transcription factors able to bind, as hetero (RAR-RXR) or homo (RXR-RXR) dimers, to specific retinoic acid response elements located in the promoter region of target genes. Two different isomers, all-trans-RA (T-RA) and 9-cis-RA (9C-RA), are the natural ligands for the RARs, whereas only 9C-RA is the natural ligand for the RXRs. The RARs and RXRs are primarily composed of two modular domains: a central DNA-binding domain (DBD) and a carboxy-terminal ligand-binding domain (LBD). In addition to its role in binding of ligands, the LBD contains dimerization motifs and an activation function 2 (AF-2) domain.

Structure Description

2lbd2lbd_x2lbd_y

In the present study, the crystal structure of the RAR-gamma LBD bound to T-RA is shown. The crystal structure reveals that the LBD folds into a three-layered alpha-helical sandwich which envelopes a hydrophobic ligand-binding pocket and has the AF-2 helix packed against the body of the receptor. Based on these observations, a mousetrap model was proposed for ligand binding and activation of RARs. In this model, the ligand would enter the pocket through the entry point left open by the AF-2 helix. With the ligand bound, the AF-2 helix would move to cover the entry of the pocket and allow the receptor to recruit coactivators.

Protein Data Bank (PDB)

References

Source

Renaud, J.P. Rochel, N. Ruff, M. Vivat, V. Chambon, P. Gronemeyer, H. Moras, D.; "Crystal structure of the RAR-gamma ligand-binding domain bound to all-trans retinoic acid."; Nature; (1995) 378:681-689 PubMed:7501014.

Others

UniProt:P22932

author: Aki Nagata


Japanese version:PDB:2LBD