Browsing by Author "Carvajal, Alonso I. I."

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    Unraveling the folding and dimerization properties of the human FoxP subfamily of transcription factors
    (2023) Villalobos, Pablo; Carvajal, Alonso I. I.; Castro-Fernandez, Victor; Babul, Jorge; Ramirez-Sarmiento, Cesar A.; Medina, Exequiel
    Human FoxP proteins share a highly conserved DNA-binding domain that dimerizes via three-dimensional domain swapping, although showing varying oligomerization propensities among its members. Here, we present an experimental and computational characterization of all human FoxP proteins to unravel how their amino acid substitutions impact their folding and dimerization mechanism. We solved the crystal structure of the forkhead domain of FoxP4 to then perform a comparison across all members, finding that their sequence changes impact not only the structural heterogeneity of their forkhead domains but also the protein-protein association energy barrier. Lastly, we demonstrate that the accumulation of a monomeric intermediate is an oligomerization-dependent feature rather than a common aspect of monomers and dimers in this protein subfamily.