Structural insight into the constitutive repression function of the nuclear receptor Rev-erbβ

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Title
Structural insight into the constitutive repression function of the nuclear receptor Rev-erbβ
Author(s)
Eui-jeon WooDae Gwin Jeong; M Y Lim; Seung Jun Kim; K J Kim; Sei Mee Yoon; Byoung Chul Park; Seong Eon Ryu
Bibliographic Citation
Journal of Molecular Biology, vol. 373, no. 3, pp. 735-744
Publication Year
2007
Abstract
The Rev-erb family is an orphan nuclear receptor acting as a negative regulator of transcription. Rev-erbα and Rev-erbβ are crucial components of the circadian clock and involved in various lipid homeostasis. They are unique nuclear receptors that lack the activation function 2 helix (AF2-helix) required for ligand-dependent activation by other members of nuclear receptors. Here, we report the crystal structure of Rev-erbβ (NR1D2) in a dimeric arrangement. The putative ligand-binding pocket (LBP) of Rev-erbβ is filled with bulky hydrophobic residues resulting in a residual cavity size that is too small to allow binding of any known ligand molecules. However, an alternative conformation of the putative LBP observed in another crystal form suggests the flexibility of this region. The kinked conformation of helix H11 allows helix H11 to bend toward helix H3 over the putative ligand binding pocket by filling and closing the cavity with its side-chains. In the absence of the AF2-helix and a cognate ligand, Rev-erbβ appears to stabilize the hydrophobic cluster in the putative ligand binding pocket and provide a structural platform for co-repressor binding by adopting the unique geometry of helix H11, a suitable conformation for the constitutive repression activity.
Keyword
constitutive repressionligand binding domainorphan receptorcrystal structureRev-erbβ
ISSN
0022-2836
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.jmb.2007.08.037
Type
Article
Appears in Collections:
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Division of Research on National Challenges > Bionanotechnology Research Center > 1. Journal Articles
Critical Diseases Diagnostics Convergence Research Center > 1. Journal Articles
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