Browsing by Author "Castro-Fernandez, Victor"

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    Structural insights into a functional unit from an immunogenic mollusk hemocyanin
    (2024) Munoz, Sebastian M.; Vallejos-Baccelliere, Gabriel; Manubens, Augusto; Salazar, Michelle L.; Nascimento, Andrey F. Z.; Tapia-Reyes, Patricio; Meneses, Claudio; Ambrosio, Andre L. B.; Becker, Maria Ines; Guixe, Victoria; Castro-Fernandez, Victor
    Mollusk hemocyanins, among the largest known proteins, are used as immunostimulants in biomedical and clinical applications. The hemocyanin of the Chilean gastropod Concholepas concholepas (CCH) exhibits unique properties, which makes it safe and effective for human immunotherapy, as observed in animal models of bladder cancer and melanoma, and dendritical cell vaccine trials. Despite its potential, the structure and amino acid sequence of CCH remain unknown. This study reports two sequence fragments of CCH, representing three complete functional units (FUs). We also determined the high -resolution (1.5 A & ring; ) X-ray crystal structure of an "FU -g type"from the CCHB subunit. This structure enables in-depth analysis of chemical interactions at the copper -binding center and unveils an unusual, truncated N-glycosylation pattern. These features are linked to eliciting more robust immunological responses in animals, offering insights into CCH's enhanced immunostimulatory properties and opening new avenues for its potential applications in biomedical research and therapies.
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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.