Structural analysis of nuclear receptors: from isolated domains to integral proteins.
Fiche publication
Date publication
janvier 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MORAS Dino, Dr ROCHEL-GUIBERTEAU Natacha
Tous les auteurs :
Brelivet Y, Rochel N, Moras D
Lien Pubmed
Résumé
Nuclear receptors (NRs) are ligand dependent transcription factors that regulate gene expression. A number of in depth structure-function relationship studies have been performed, in particular with drug design perspectives. Recent structural results concerning integral receptors in diverse functional states, obtained using a combination of different methods, now allow a better understanding of the mechanisms involved in molecular regulation. The structural data highlight the importance of DNA sequences for binding selectivity and the role of promoter response elements in the spatial organization of the protein domains into functional complexes. The solution structures of several heterodimer complexes reveal how the DNA directs the positioning of coactivators. In the case of PPARgamma-RXRalpha the comparison with the crystal structure reveals two different conformational states that illustrate the flexibility of the receptors. The results shed light on the dynamics of the molecular recognition process.
Référence
Mol Cell Endocrinol. 2012 Jan 30;348(2):466-73