Batista, Fernanda A. H.
Neto, Mario de Oliveira
Figueira, Ana Carolina M.
Palma, Mario S.
Número total de Autores: 8
Afiliação do(s) autor(es):
 Univ Sao Paulo, Inst Phys Sao Carlos, Sao Paulo - Brazil
 CNPEM, Natl Lab Biosci, Sao Paulo - Brazil
 Methodist Hosp, Ctr Diabet, Houston, TX 77030 - USA
 Methodist Hosp, Canc Res Unit, Houston, TX 77030 - USA
 Univ Estadual Sao Paulo UNESP, Inst Biosci Rio Claro, Dept Biol, Ctr Study Social Insects CEIS, Sao Paulo - Brazil
 Natl Inst Sci & Technol Immunol INCT Iii, Sao Paulo - Brazil
Número total de Afiliações: 6
Tipo de documento:
FEB 21 2012.
Citações Web of Science:
The peroxisome proliferator-activated receptors (PPARs) regulate genes involved in lipid and carbohydrate metabolism, and are targets of drugs approved for human use. Whereas the crystallographic structure of the complex of full length PPAR gamma and RXR alpha is known, structural alterations induced by heterodimer formation and DNA contacts are not well understood. Herein, we report a small-angle X-ray scattering analysis of the oligomeric state of hPPAR gamma alone and in the presence of retinoid X receptor (RXR). The results reveal that, in contrast with other studied nuclear receptors, which predominantly form dimers in solution, hPPAR gamma remains in the monomeric form by itself but forms heterodimers with hRXR alpha. The low-resolution models of hPPAR gamma/RXR alpha complexes predict significant changes in opening angle between heterodimerization partners (LBD) and extended and asymmetric shape of the dimer (LBD-DBD) as compared with X-ray structure of the full-length receptor bound to DNA. These differences between our SAXS models and the high-resolution crystallographic structure might suggest that there are different conformations of functional heterodimer complex in solution. Accordingly, hydrogen/deuterium exchange experiments reveal that the heterodimer binding to DNA promotes more compact and less solvent-accessible conformation of the receptor complex. (AU)