scholarly journals A comprehensive structural and functional analysis of the ligand binding domain of the nuclear receptor superfamily reveals highly conserved signaling motifs and two distinct canonical forms through evolution

2020 ◽  
Author(s):  
Thanasis Mitsis ◽  
Louis Papageorgiou ◽  
Aspasia Efthimiadou ◽  
Flora Bacopoulou ◽  
Dimitrios Vlachakis ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Ligand Binding ◽  
Nuclear Receptor ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Canonical Forms ◽  
Nuclear Receptor Superfamily

scholarly journals Novel Mechanism of Nuclear Receptor Corepressor Interaction Dictated by Activation Function 2 Helix Determinants

2002 ◽  
Vol 22 (19) ◽  
pp. 6831-6841 ◽  
Author(s):  
Anna N. Moraitis ◽  
Vincent Giguère ◽  
Catherine C. Thompson
Keyword(s):  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Ligand Binding ◽  
Nuclear Receptor ◽  
Thyroid Hormone Receptor ◽  
Activation Function ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Cerebellar Development ◽  
Nuclear Receptor Corepressor

ABSTRACT Transcriptional regulation by nuclear receptors is controlled by the concerted action of coactivator and corepressor proteins. The product of the thyroid hormone-regulated mammalian gene hairless (Hr) was recently shown to function as a thyroid hormone receptor corepressor. Here we report that Hr acts as a potent repressor of transcriptional activation by RORα, an orphan nuclear receptor essential for cerebellar development. In contrast to other corepressor-nuclear receptor interactions, Hr binding to RORα is mediated by two LXXLL-containing motifs, a mechanism associated with coactivator interaction. Mutagenesis of conserved amino acids in the ligand binding domain indicates that RORα activity is ligand-dependent, suggesting that corepressor activity is maintained in the presence of ligand. Despite similar recognition helices shared with coactivators, Hr does not compete for the same molecular determinants at the surface of the RORα ligand binding domain, indicating that Hr-mediated repression is not simply through displacement of coactivators. Remarkably, the specificity of Hr corepressor action can be transferred to a retinoic acid receptor by exchanging the activation function 2 (AF-2) helix. Repression of the chimeric receptor is observed in the presence of retinoic acid, demonstrating that in this context, Hr is indeed a ligand-oblivious nuclear receptor corepressor. These results suggest a novel molecular mechanism for corepressor action and demonstrate that the AF-2 helix can play a dynamic role in controlling corepressor as well as coactivator interactions. The interaction of Hr with RORα provides direct evidence for the convergence of thyroid hormone and RORα-mediated pathways in cerebellar development.

Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-α

Nature ◽  
1995 ◽  
Vol 375 (6530) ◽  
pp. 377-382 ◽  
Author(s):  
William Bourguet ◽  
Marc Ruff ◽  
Pierre Chambon ◽  
Hinrich Gronemeyer ◽  
Dino Moras
Keyword(s):  
Crystal Structure ◽  
Ligand Binding ◽  
Nuclear Receptor ◽  
Binding Domain ◽  
Ligand Binding Domain

scholarly journals The Crystal Structure of the Orphan Nuclear Receptor NR2E3/PNR Ligand Binding Domain Reveals a Dimeric Auto-Repressed Conformation

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e74359 ◽  
Author(s):  
M. H. Eileen Tan ◽  
X. Edward Zhou ◽  
Fen-Fen Soon ◽  
Xiaodan Li ◽  
Jun Li ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Ligand Binding ◽  
Nuclear Receptor ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Orphan Nuclear Receptor

scholarly journals Structural and Functional Insights into the Ligand-binding Domain of a Nonduplicated Retinoid X Nuclear Receptor from the Invertebrate Chordate Amphioxus

2008 ◽  
Vol 284 (3) ◽  
pp. 1938-1948 ◽  
Author(s):  
Giuseppe D. Tocchini-Valentini ◽  
Natacha Rochel ◽  
Hector Escriva ◽  
Pierre Germain ◽  
Carole Peluso-Iltis ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Nuclear Receptor ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Invertebrate Chordate

scholarly journals Detection of the TCDD Binding-Fingerprint within the Ah Receptor Ligand Binding Domain by Structurally Driven Mutagenesis and Functional Analysis

Biochemistry ◽  
2009 ◽  
Vol 48 (25) ◽  
pp. 5972-5983 ◽  
Author(s):  
Alessandro Pandini ◽  
Anatoly A. Soshilov ◽  
Yujuan Song ◽  
Jing Zhao ◽  
Laura Bonati ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Ligand Binding ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Ah Receptor ◽  
Receptor Ligand
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