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Conformational Stability andDNA Binding Specificity of the Cardiac T-Box Transcription Factor Tbx20

Citation

Macindoe, I and Glockner, L and Vukasin, P and Stennard, FA and Costa, MW and Harvey, RP and Mackay, JP and Sunde, M, Conformational Stability andDNA Binding Specificity of the Cardiac T-Box Transcription Factor Tbx20, Journal of Molecular Biology, 389 pp. 606-618. ISSN 0022-2836 (2009) [Refereed Article]

Copyright Statement

Copyright 2009 Elsevier Ltd.

DOI: doi:10.1016/j.jmb.2009.04.056

Abstract

The transcription factor Tbx20 acts within a hierarchy of T-box factors in lineage specification and morphogenesis in the mammalian heart and is mutated in congenital heart disease. T-box family members share a ∼20-kDa DNA-binding domain termed the T-box. The question of how highly homologous T-box proteins achieve differential transcriptional control in heart development, while apparently binding to the same DNA sequence, remains unresolved. Here we show that the optimal DNA recognition sequence for the T-box of Tbx20 corresponds to a T-half-site. Furthermore, we demonstrate using purified recombinant domains that distinct T-boxes show significant differences in the affinity and kinetics of binding and in conformational stability, with the T-box of Tbx20 displaying molten globule character. Our data highlight unique features of Tbx20 and suggest mechanistic ways in which cardiac T-box factors might interact synergistically and/or competitively within the cardiac regulatory network

Item Details

Item Type:Refereed Article
Keywords:T-box transcrition factor
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Biochemistry and Cell Biology not elsewhere classified
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Environmental Sciences
Author:Stennard, FA (Dr Fiona Stennard)
ID Code:99852
Year Published:2009
Web of Science® Times Cited:19
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-04-13
Last Modified:2015-05-05
Downloads:0

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