Structural analysis of nuclear receptors: From isolated domains to integral proteins
Abstract
Nuclear receptors (NRs) are ligand dependent transcription factors that regulate gene expression. A number of in depth structure-function relationship studies have been performed, in particular with drug design perspectives. Recent structural results concerning integral receptors in diverse functional states, obtained using a combination of different methods, now allow a better understanding of the mechanisms involved in molecular regulation. The structural data highlight the importance of DNA sequences for binding selectivity and the role of promoter response elements in the spatial organization of the protein domains into functional complexes. The solution structures of several heterodimer complexes reveal how the DNA directs the positioning of coactivators. In the case of PPARγ-RXRα the comparison with the crystal structure reveals two different conformational states that illustrate the flexibility of the receptors. The results shed light on the dynamics of the molecular recognition process.
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Only one coactivator molecule is recruited by the heterodimer through the RAR partner, and the architecture of the DNA-bound receptor complexes orients the coactivator on one side of the DNA opposite to the RXR LBD and DBD so that it can reach its targets, the histone tails.
“According to recent studies ( 87,97 ), only one coactivator molecule is recruited by the heterodimer through the RAR partner, and the architecture of the DNA-bound receptor complexes orients the coactivator on one side of the DNA opposite to the RXR LBD and DBD so that it can reach its targets, the histone tails.”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [87]
Upon ligand binding, RARα undergoes conformational changes that provoke corepressor release and coactivator binding.
“Nevertheless, upon ligand binding, RAR ␣ undergoes conformational changes that provoke corepressor release and coactivator binding ( Fig. 3B ).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [87]
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Retinoic acid receptors: From molecular mechanisms to cancer therapy
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Self-citation
- Authors
- Brélivet, Y., Rochel, N., & Moras, D.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Moras, Dino
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 348
- Issue
- 2
- Pages
- 466-473
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W2015927691
- Cited by
- 64
- References
- 6
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 8 · 2014: 10 · 2013: 7 · 2012: 3
- FWCI
- 0.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- nuclear receptors, transcription factors, receptor structure-function, DNA binding selectivity, promoter response elements, coactivator binding, conformational flexibility, molecular recognition, solution structure, crystal structure
- MeSH terms
- Base Sequence, Binding Sites, DNA, Gene Expression Regulation, Humans, Models, Molecular, Protein Binding, Receptors, Cytoplasmic and Nuclear, Macromolecular Substances, Protein Interaction Domains and Motifs, Co-Repressor Proteins
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