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

journal contribution
posted on 2023-05-18, 09:13 authored by Macindoe, I, Glockner, L, Vukasin, P, Fiona StennardFiona Stennard, Costa, MW, Harvey, RP, Mackay, JP, Sunde, M
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


Publication title

Journal of Molecular Biology








Menzies Institute for Medical Research


Academic Press Ltd Elsevier Science Ltd

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24-28 Oval Rd, London, England, Nw1 7Dx

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Copyright 2009 Elsevier Ltd.

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Expanding knowledge in the environmental sciences

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