4NQA

Crystal structure of liganded hRXR-alpha/hLXR-beta heterodimer on DNA

Summary for 4NQA

• Entry DOI: 10.2210/pdb4nqa/pdb
• Descriptor: Retinoic acid receptor RXR-alpha, Liver X nuclear receptor beta, Nuclear receptor coactivator 2, ... (8 entities in total)
• Functional Keywords: multi-domain, rxr, lxr, dbd, lbd, ligand, zinc finger, transcription regulator-dna complex, transcription regulator/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : P19793 F1D8P7 Q15596
• Total number of polymer chains: 12
• Total formula weight: 201035.72

Authors

Lou, X.H.,Toresson, G.,Benod, C.,Suh, J.H.,Phillips, K.J.,Webb, P.,Gustafsson, J.A. (deposition date: 2013-11-24, release date: 2014-02-26, Last modification date: 2024-02-28)

Primary citation

Lou, X.,Toresson, G.,Benod, C.,Suh, J.H.,Philips, K.J.,Webb, P.,Gustafsson, J.A.
Structure of the retinoid X receptor alpha-liver X receptor beta (RXR alpha-LXR beta ) heterodimer on DNA.
Nat.Struct.Mol.Biol., 21:277-281, 2014

PubMed Abstract: Nuclear receptors (NRs) are conditional transcription factors with common multidomain organization that bind diverse DNA elements. How DNA sequences influence NR conformation is poorly understood. Here we report the crystal structure of the human retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on its cognate element, an AGGTCA direct repeat spaced by 4 nt. The complex has an extended X-shaped arrangement, with DNA- and ligand-binding domains crossed, in contrast to the parallel domain arrangement of other NRs that bind an AGGTCA direct repeat spaced by 1 nt. The LXRβ core binds DNA via canonical contacts and auxiliary DNA contacts that enhance affinity for the response element. Comparisons of RXRα-LXRβs in the crystal asymmetric unit and with previous NR structures reveal flexibility in NR organization and suggest a role for RXRα in adaptation of heterodimeric complexes to DNA.

PubMed: 24561505
DOI: 10.1038/nsmb.2778

Experimental method

X-RAY DIFFRACTION (3.102 Å)