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.
PPAR Res. 2012;2012:701412. doi: 10.1155/2012/701412. Epub 2012 Dec 18.
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.
过氧化物酶体增殖物激活受体 γ（PPARγ）是葡萄糖内稳态和胰岛素敏感性的关键调节因子。PPARγ 必须与其二聚体伙伴视黄酸 X 受体（RXR）异二聚化，以结合 DNA 及其相关共激活因子，如 p160 家族成员或 PGC-1α，从而调节基因网络。为了了解共激活因子如何被功能性异二聚体 PPARγ/RXRα 识别，并确定复合物的拓扑结构，我们使用小角度 X 射线散射技术对结合调控基因 DNA 的 PPARγ/RXRα 进行了结构研究，同时还研究了 TIF2 受体相互作用结构域（RID）。溶液结构揭示了整体结构的不对称性，这是由于 DNA 在定位异二聚体中的关键作用所致，并表明 TIF2 对异二聚体的不对称结合。
