On the Spectrum with T‐box Brain Protein 1: A Transcription Factor Protein Critical for Normal Neural Development

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The Independent School MSOE Center for BioMolecular Modeling SMART Team used 3‐D modeling and printing technology to examine structure‐function relationships and applications of T‐box brain protein 1 (TBR1). The overall function of TBR1 is to act as a transcription factor protein. Located in the nucleus, this protein aids in vertebrate embryonic brain and neural development, specifically acting as an essential component in cerebral cortex development. TBR1 has the same general structure as other transcription factor protein homologs of the T‐box family, which all share a common DNA‐binding motif (the T‐box) and can form homodimers. Structurally, TBR1 has been studied to show how specific residues in its active site could lead to autism spectrum disorders (among other neurological diseases) if it does not align properly with DNA during transcription. Within the T‐box domain at Position 271, a tryptophan sidechain is located in the center of the motif that stabilizes the domain through contact with surrounding hydrophobic amino acids and ensures that DNA‐binding residues are correctly positioned. At Position 374, an asparagine residue also stabilizes the domain and ensures that DNA‐binding sites are positioned correctly by forming hydrogen bonds with its surrounding residues. Studies suggest that positively‐charged lysine amino acids that are close to the negatively‐charged phosphate backbone of DNA, such as those at Position 288 and Position 389, are critical for the binding of the protein to the minor groove of DNA. Additionally, TBR1 has been shown to act as either a repressor or activator in gene regulation of several important neurological cascades. Therefore, while not all the mechanisms are understood and many of its applications are still theoretical at this time, TBR1 has been shown to be involved with attention and memory. When this transcription factor protein malfunctions, its deregulation has been linked to Parkinson's disease and Alzheimer's disease. It has also been linked to several autism‐related disorder genes and a small percentage of unrelated sporadic autism disorders. Finally, TBR1 may be linked to language and speech disorders and synesthesia, though more research must be conducted to understand its exact function in these areas.Support or Funding InformationSupported and Funded by The Independent School; Wichita, KS 67207This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.