ArticleBiophysical journal2013
Dynamics of nuclear receptor Helix-12 switch of transcription activation by modeling time-resolved fluorescence anisotropy decays.
Article in Biophysical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 41 citations in OpenAlex.
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- Look What You Made Me Do: Discerning Feature for Classification of Endocrine-Disrupting Chemical Binding to Steroid Hormone Receptors.Journal of chemical information and modeling · 2025Article
- Illuminating ligand-induced dynamics in nuclear receptors through MD simulations.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024Review
- Retinoid X Receptor: Cellular and Biochemical Roles of Nuclear Receptor with a Focus on Neuropathological Involvement.Molecular neurobiology · 2022Review
- To Probe Full and Partial Activation of Human Peroxisome Proliferator-Activated Receptors by Pan-Agonist Chiglitazar Using Molecular Dynamics Simulations.PPAR research · 2020Article
- Computational investigations of the binding mechanism of novel benzophenone imine inhibitors for the treatment of breast cancer.RSC advances · 2019Article
- Ligand Binding Induces Agonistic-Like Conformational Adaptations in Helix 12 of Progesterone Receptor Ligand Binding Domain.Frontiers in chemistry · 2019Article
- Structural and Dynamic Elucidation of a Non-acid PPARNuclear receptor research · 2018Article
- An alternative conformation of ERβ bound to estradiol reveals H12 in a stable antagonist position.Scientific reports · 2017Article
- Probing conformational dynamics of an enzymatic active site by an in situ single fluorogenic probe under piconewton force manipulation.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Unexpected Allosteric Network Contributes to LRH-1 Co-regulator Selectivity.The Journal of biological chemistry · 2016Article
- Exploring Flexibility of Progesterone Receptor Ligand Binding Domain Using Molecular Dynamics.PloS one · 2016Article
- Structural and Dynamical Insight into PPARγ Antagonism: In Silico Study of the Ligand-Receptor Interactions of Non-Covalent Antagonists.International journal of molecular sciences · 2015Article
- Single-molecule enzymatic conformational dynamics: spilling out the product molecules.The journal of physical chemistry. B · 2014Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear hormone receptors (NRs) are major targets for pharmaceutical development. Many experiments demonstrate that their C-terminal Helix (H12) is more flexible in the ligand-binding domains (LBDs) without ligand, this increased mobility being correlated with transcription repression and human diseases. Crystal structures have been obtained in which the H12 is extended, suggesting the possibility of large amplitude H12 motions in solution. However, these structures were interpreted as possible crystallographic artifacts, and thus the microscopic nature of H12 movements is not well known. To bridge the gap between experiments and molecular models and provide a definitive picture of H12 motions in solution, extensive molecular dynamics simulations of the peroxisome proliferator-activated receptor-γ LBD, in which the H12 was bound to a fluorescent probe, were performed. A direct comparison of the modeled anisotropy decays to time-resolved fluorescence anisotropy experiments was obtained. It is shown that the decay rates are dependent on the interactions of the probe with the surface of the protein, and display little correlation with the flexibility of the H12. Nevertheless, for the probe to interact with the surface of the LBD, the H12 must be folded over the body of the LBD. Therefore, the molecular mobility of the H12 should preserve the globularity of the LBD, so that ligand binding and dissociation occur by diffusion through the surface of a compact receptor. These results advance the comprehension of both ligand-bound and ligand-free receptor structures in solution, and also guide the interpretation of time-resolved anisotropy decays from a molecular perspective, particularly by the use of simulations.
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