2q81

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==Overview==
==Overview==
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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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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.
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
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A Beta-Sheet Interaction Interface Directs the Tetramerisation of the Miz-1 POZ Domain., Stead MA, Trinh CH, Garnett JA, Carr SB, Baron AJ, Edwards TA, Wright SC, J Mol Biol. 2007 Nov 2;373(4):820-6. Epub 2007 Aug 21. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17880999 17880999]
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A beta-sheet interaction interface directs the tetramerisation of the Miz-1 POZ domain., Stead MA, Trinh CH, Garnett JA, Carr SB, Baron AJ, Edwards TA, Wright SC, J Mol Biol. 2007 Nov 2;373(4):820-6. Epub 2007 Aug 21. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17880999 17880999]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Carr, S.B.]]
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[[Category: Carr, S B.]]
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[[Category: Edwards, T.A.]]
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[[Category: Edwards, T A.]]
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[[Category: Garnett, J.A.]]
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[[Category: Garnett, J A.]]
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[[Category: Stead, M.A.]]
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[[Category: Stead, M A.]]
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[[Category: Trinh, C.H.]]
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[[Category: Trinh, C H.]]
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[[Category: Wright, S.C.]]
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[[Category: Wright, S C.]]
[[Category: PG4]]
[[Category: PG4]]
[[Category: btb/poz domain]]
[[Category: btb/poz domain]]
[[Category: transcription]]
[[Category: transcription]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:22:35 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:37:00 2008''

Revision as of 16:37, 21 February 2008


2q81, resolution 2.100Å

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Crystal Structure of the Miz-1 BTB/POZ domain

Overview

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.

About this Structure

2Q81 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

Reference

A beta-sheet interaction interface directs the tetramerisation of the Miz-1 POZ domain., Stead MA, Trinh CH, Garnett JA, Carr SB, Baron AJ, Edwards TA, Wright SC, J Mol Biol. 2007 Nov 2;373(4):820-6. Epub 2007 Aug 21. PMID:17880999

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