2Q81

A Beta-Sheet Interaction Interface Directs the Tetramerisation of the Miz-1 POZ Domain

(2007) J Mol Biol 373: 820-826

• PubMed: 17880999 Search on PubMed
• DOI: https://doi.org/10.1016/j.jmb.2007.08.026
• Primary Citation of Related Structures:  
  2Q81


• PubMed 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 A 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.

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Organizational Affiliation: 

Molecular Cell Biology Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Garstang/Astbury Buildings, Leeds LS2 9JT, UK.