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Solution Structures of PPARγ2/RXRα Complexes.

Osz J, Pethoukhov MV, Sirigu S, Svergun DI, Moras D, Rochel N - PPAR Res (2012)

Bottom Line: PPARγ is a key regulator of glucose homeostasis and insulin sensitization.PPARγ must heterodimerize with its dimeric partner, the retinoid X receptor (RXR), to bind DNA and associated coactivators such as p160 family members or PGC-1α to regulate gene networks.The solution structures reveal an asymmetry of the overall structure due to the crucial role of the DNA in positioning the heterodimer and indicate asymmetrical binding of TIF2 to the heterodimer.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre National de Recherche Scientifique (CNRS) UMR 7104, Institut National de Santé et de Recherche Médicale (INSERM) U964, Université de Strasbourg, 67404 Illkirch, France.

ABSTRACT
PPARγ is a key regulator of glucose homeostasis and insulin sensitization. PPARγ must heterodimerize with its dimeric partner, the retinoid X receptor (RXR), to bind DNA and associated coactivators such as p160 family members or PGC-1α to regulate gene networks. To understand how coactivators are recognized by the functional heterodimer PPARγ/RXRα and to determine the topological organization of the complexes, we performed a structural study using small angle X-ray scattering of PPARγ/RXRα in complex with DNA from regulated gene and the TIF2 receptor interacting domain (RID). The solution structures reveal an asymmetry of the overall structure due to the crucial role of the DNA in positioning the heterodimer and indicate asymmetrical binding of TIF2 to the heterodimer.

No MeSH data available.


Related in: MedlinePlus

Experimental SAXS data of PPARγ/RXRα LBDs complexes. (a) Scattering profiles of PPARγ/RXRα LBDs (red) and TIF2 RID/PPARγ/RXRα LBDs (pink). (b) Distance distribution functions computed from the X-ray scattering patterns using the program GNOM. Same color code as in (a). (c) Kratky representations for TIF2 RID (blue) and TIF2 RID/PPARγ/RXRα LBDs (green).
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fig2: Experimental SAXS data of PPARγ/RXRα LBDs complexes. (a) Scattering profiles of PPARγ/RXRα LBDs (red) and TIF2 RID/PPARγ/RXRα LBDs (pink). (b) Distance distribution functions computed from the X-ray scattering patterns using the program GNOM. Same color code as in (a). (c) Kratky representations for TIF2 RID (blue) and TIF2 RID/PPARγ/RXRα LBDs (green).

Mentions: As a reference, scattering profiles of PPARγ/RXRα LBDs alone were collected (Figure 2(a)). Monodisperse concentrated solutions of PPARγ/RXRα LBDs were measured, and the structural parameters including the radius of gyration (Rg) and the maximum particle dimension (Dmax⁡) were computed from the experimental scattering patterns from the heterodimer (Table 1). A symmetrical pair-distribution function is observed (Figure 2(b)) indicating a globular complex. The experimental SAXS data is well fitted by the scattering profile calculated from the crystal structure (PDB ID: 3H0A) using CRYSOL [23] and is in agreement with SAXS parameters measured for heterodimer LBDs [17, 18].


Solution Structures of PPARγ2/RXRα Complexes.

Osz J, Pethoukhov MV, Sirigu S, Svergun DI, Moras D, Rochel N - PPAR Res (2012)

Experimental SAXS data of PPARγ/RXRα LBDs complexes. (a) Scattering profiles of PPARγ/RXRα LBDs (red) and TIF2 RID/PPARγ/RXRα LBDs (pink). (b) Distance distribution functions computed from the X-ray scattering patterns using the program GNOM. Same color code as in (a). (c) Kratky representations for TIF2 RID (blue) and TIF2 RID/PPARγ/RXRα LBDs (green).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig2: Experimental SAXS data of PPARγ/RXRα LBDs complexes. (a) Scattering profiles of PPARγ/RXRα LBDs (red) and TIF2 RID/PPARγ/RXRα LBDs (pink). (b) Distance distribution functions computed from the X-ray scattering patterns using the program GNOM. Same color code as in (a). (c) Kratky representations for TIF2 RID (blue) and TIF2 RID/PPARγ/RXRα LBDs (green).
Mentions: As a reference, scattering profiles of PPARγ/RXRα LBDs alone were collected (Figure 2(a)). Monodisperse concentrated solutions of PPARγ/RXRα LBDs were measured, and the structural parameters including the radius of gyration (Rg) and the maximum particle dimension (Dmax⁡) were computed from the experimental scattering patterns from the heterodimer (Table 1). A symmetrical pair-distribution function is observed (Figure 2(b)) indicating a globular complex. The experimental SAXS data is well fitted by the scattering profile calculated from the crystal structure (PDB ID: 3H0A) using CRYSOL [23] and is in agreement with SAXS parameters measured for heterodimer LBDs [17, 18].

Bottom Line: PPARγ is a key regulator of glucose homeostasis and insulin sensitization.PPARγ must heterodimerize with its dimeric partner, the retinoid X receptor (RXR), to bind DNA and associated coactivators such as p160 family members or PGC-1α to regulate gene networks.The solution structures reveal an asymmetry of the overall structure due to the crucial role of the DNA in positioning the heterodimer and indicate asymmetrical binding of TIF2 to the heterodimer.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre National de Recherche Scientifique (CNRS) UMR 7104, Institut National de Santé et de Recherche Médicale (INSERM) U964, Université de Strasbourg, 67404 Illkirch, France.

ABSTRACT
PPARγ is a key regulator of glucose homeostasis and insulin sensitization. PPARγ must heterodimerize with its dimeric partner, the retinoid X receptor (RXR), to bind DNA and associated coactivators such as p160 family members or PGC-1α to regulate gene networks. To understand how coactivators are recognized by the functional heterodimer PPARγ/RXRα and to determine the topological organization of the complexes, we performed a structural study using small angle X-ray scattering of PPARγ/RXRα in complex with DNA from regulated gene and the TIF2 receptor interacting domain (RID). The solution structures reveal an asymmetry of the overall structure due to the crucial role of the DNA in positioning the heterodimer and indicate asymmetrical binding of TIF2 to the heterodimer.

No MeSH data available.


Related in: MedlinePlus