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Structure of the intact PPAR-γ–RXR-α nuclear receptor complex on DNA.

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Title: Structure of the intact PPAR-γ–RXR-α nuclear receptor complex on DNA.
Authors: Chandra, Vikas, Huang, Pengxiang, Hamuro, Yoshitomo, Raghuram, Srilatha, Wang, Yongjun, Burris, Thomas P., Rastinejad, Fraydoon
Source: Nature. 11/20/2008, Vol. 456 Issue 7220, p350-356. 7p. 5 Diagrams.
Subjects: Molecular structure, Nuclear receptors (Biochemistry), Gene expression, Transcription factors, Ligand binding (Biochemistry), DNA-binding proteins, Peroxisomes, Scientific method
Abstract: Nuclear receptors are multi-domain transcription factors that bind to DNA elements from which they regulate gene expression. The peroxisome proliferator-activated receptors (PPARs) form heterodimers with the retinoid X receptor (RXR), and PPAR-γ has been intensively studied as a drug target because of its link to insulin sensitization. Previous structural studies have focused on isolated DNA or ligand-binding segments, with no demonstration of how multiple domains cooperate to modulate receptor properties. Here we present structures of intact PPAR-γ and RXR-α as a heterodimer bound to DNA, ligands and coactivator peptides. PPAR-γ and RXR-α form a non-symmetric complex, allowing the ligand-binding domain (LBD) of PPAR-γ to contact multiple domains in both proteins. Three interfaces link PPAR-γ and RXR-α, including some that are DNA dependent. The PPAR-γ LBD cooperates with both DNA-binding domains (DBDs) to enhance response-element binding. The A/B segments are highly dynamic, lacking folded substructures despite their gene-activation properties. [ABSTRACT FROM AUTHOR]
Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Structure of the intact PPAR-γ–RXR-α nuclear receptor complex on DNA.
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  Data: Nuclear receptors are multi-domain transcription factors that bind to DNA elements from which they regulate gene expression. The peroxisome proliferator-activated receptors (PPARs) form heterodimers with the retinoid X receptor (RXR), and PPAR-γ has been intensively studied as a drug target because of its link to insulin sensitization. Previous structural studies have focused on isolated DNA or ligand-binding segments, with no demonstration of how multiple domains cooperate to modulate receptor properties. Here we present structures of intact PPAR-γ and RXR-α as a heterodimer bound to DNA, ligands and coactivator peptides. PPAR-γ and RXR-α form a non-symmetric complex, allowing the ligand-binding domain (LBD) of PPAR-γ to contact multiple domains in both proteins. Three interfaces link PPAR-γ and RXR-α, including some that are DNA dependent. The PPAR-γ LBD cooperates with both DNA-binding domains (DBDs) to enhance response-element binding. The A/B segments are highly dynamic, lacking folded substructures despite their gene-activation properties. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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