Stead, MA, Trinh, CH, Garnett, JA et al. (4 more authors) (2007) A beta-sheet interaction interface directs the tetramerisation of the Miz-1 POZ domain. Journal of Molecular Biology, 373 (4). 820 - 826. ISSN 0022-2836
Abstract
The POZ/BTB domain is an evolutionarily conserved motif found in approximately 40 zinc-finger transcription factors (POZ-ZF factors). Several POZ-ZF factors are implicated in human cancer, and POZ domain interaction interfaces represent an attractive target for therapeutic intervention. Miz-1 (Myc-interacting zinc-finger protein) is a POZ-ZF factor that regulates DNA-damage-induced cell cycle arrest and plays an important role in human cancer by virtue of its interaction with the c-Myc and BCL6 oncogene products. The Miz-1 POZ domain mediates both self-association and the recruitment of non-POZ partners. POZ-ZF factors generally function as homodimers, although higher-order associations and heteromeric interactions are known to be physiologically important; crucially, the interaction interfaces in such large complexes have not been characterised. We report here the crystal structure of the Miz-1 POZ domain up to 2.1 Å resolution. The tetrameric organisation of Miz-1 POZ reveals two types of interaction interface between subunits; an interface of alpha-helices resembles the dimerisation interface of reported POZ domain structures, whereas a novel beta-sheet interface directs the association of two POZ domain dimers. We show that the beta-sheet interface directs the tetramerisation of the Miz-1 POZ domain in solution and therefore represents a newly described candidate interface for the higher-order homo- and hetero-oligomerisation of POZ-ZF proteins in vivo.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2007, Elsevier. This is an author produced version of a paper published in Journal of Molecular Biology. Uploaded in accordance with the publisher's self-archiving policy. NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Molecular Biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Molecular Biology ,373 (4) , (2007) DOI http://dx.doi.org/10.1016/j.jmb.2007.08.026 |
Keywords: | BCL6; BTB domain; c-Myc |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 11 Jul 2014 11:46 |
Last Modified: | 16 Nov 2016 10:59 |
Published Version: | http://dx.doi.org/10.1016/j.jmb.2007.08.026 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.jmb.2007.08.026 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:79624 |