2v0v

From Proteopedia

Revision as of 10:45, 23 January 2008

CRYSTAL STRUCTURE OF REV-ERB BETA

Overview

The Rev-erb family is an orphan nuclear receptor acting as a negative, regulator of transcription. Rev-erbalpha and Rev-erbbeta 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-erbbeta (NR1D2) in a dimeric arrangement. The putative, ligand-binding pocket (LBP) of Rev-erbbeta 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-erbbeta 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.

About this Structure

2V0V is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural Insight into the Constitutive Repression Function of the Nuclear Receptor Rev-erbbeta., Woo EJ, Jeong DG, Lim MY, Jun Kim S, Kim KJ, Yoon SM, Park BC, Eon Ryu S, J Mol Biol. 2007 Oct 26;373(3):735-44. Epub 2007 Aug 22. PMID:17870090

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