The influence of various regions of the FOXP2 sequence on its structure and DNA binding function
| Autor: | Monare Thulo, Ashleigh Blane, Sylvia Fanucchi, Heather L Donald, Megan A Rabie, Naadira Pahad, Cardon M Perumal, J. Carlos Penedo |
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| Přispěvatelé: | University of St Andrews. School of Physics and Astronomy, University of St Andrews. Centre for Biophotonics, University of St Andrews. Biomedical Sciences Research Complex |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Leucine zipper QH301 Biology Biophysics NDAS Forkhead domain QH426 Genetics FOX proteins Biochemistry 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship QH301 Transcriptional regulation Biopolymers Protein Domains Transcription (biology) oligomerisation Transcription factors Oligomerization DNA binding Molecular Biology Transcription factor QH426 Research Articles Zinc finger Leucine Zippers 030102 biochemistry & molecular biology Molecular Interactions Chemistry Circular Dichroism FOXP2 Forkhead Transcription Factors Cell Biology FOXP1 DNA Transcription regulation Cell biology 030104 developmental biology Spectrometry Fluorescence Chromatography Gel Spectrophotometry Ultraviolet FOXP Protein Binding Forkhead |
| Zdroj: | Bioscience Reports |
| Popis: | Funding: University of the Witwatersrand, South African National Research Foundation Grant 80681 to S.F., Grant 68898 to H.W.D., the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation Grant 64788 to H.W.D., the Medical Research Council of South Africa and the Royal Society Grant NAF/R2/180787 to SF. FOX proteins are a superfamily of transcription factors which share a DNA-binding domain referred to as the forkhead domain. Our focus is on the FOXP subfamily members, which are involved in language and cognition amongst other things. The FOXP proteins contain a conserved zinc finger and a leucine zipper motif in addition to the forkhead domain. The remainder of the sequence is predicted to be unstructured and includes an acidic C-terminal tail. In the present study, we aim to investigate how both the structured and unstructured regions of the sequence cooperate so as to enable FOXP proteins to perform their function. We do this by studying the effect of these regions on both oligomerisation and DNA binding. Structurally, the FOXP proteins appear to be comparatively globular with a high proportion of helical structure. The proteins multimerise via the leucine zipper, and the stability of the multimers is controlled by the unstructured interlinking sequence including the acid rich tail. FOXP2 is more compact than FOXP1, has a greater propensity to form higher order oligomers, and binds DNA with stronger affinity. We conclude that while the forkhead domain is necessary for DNA binding, the affinity of the binding event is attributable to the leucine zipper, and the unstructured regions play a significant role in the specificity of binding. The acid rich tail forms specific contacts with the forkhead domain which may influence oligomerisation and DNA binding, and therefore the acid rich tail may play an important regulatory role in FOXP transcription. Publisher PDF |
| Databáze: | OpenAIRE |
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