Browsing by Author "Villalobos, Pablo"

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    Human FoxP Transcription Factors as Tractable Models of the Evolution and Functional Outcomes of Three-Dimensional Domain Swapping
    (2021) Villalobos, Pablo; Ramirez Sarmiento, Cesar A.; Babul, Jorge; Medina, Exequiel
    The association of two or more proteins to adopt a quaternary complex is one of the most widespread mechanisms by which protein function is modulated. In this scenario, three-dimensional domain swapping (3D-DS) constitutes one plausible pathway for the evolution of protein oligomerization that exploits readily available intramolecular contacts to be established in an intermolecular fashion. However, analysis of the oligomerization kinetics and thermodynamics of most extant 3D-DS proteins shows its dependence on protein unfolding, obscuring the elucidation of the emergence of 3D-DS during evolution, its occurrence under physiological conditions, and its biological relevance. Here, we describe the human FoxP subfamily of transcription factors as a feasible model to study the evolution of 3D-DS, due to their significantly faster dissociation and dimerization kinetics and lower dissociation constants in comparison to most 3D-DS models. Through the biophysical and functional characterization of FoxP proteins, relevant structural aspects highlighting the evolutionary adaptations of these proteins to enable efficient 3D-DS have been ascertained. Most biophysical studies on FoxP suggest that the dynamics of the polypeptide chain are crucial to decrease the energy barrier of 3D-DS, enabling its fast oligomerization under physiological conditions. Moreover, comparison of biophysical parameters between human FoxP proteins in the context of their minute sequence differences suggests differential evolutionary strategies to favor homoassociation and presages the possibility of heteroassociations, with direct impacts in their gene regulation function.
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    Indigenous tourism, crisis and resilience in times of COVID-19: theoretical and methodological approaches from Chile
    (2023) Maza, Francisca de la; Ried, Andrés; Odone C., María Carolina; Le Moigne, Jean Philippe; Villalobos, Pablo; Meneses, Katherine
    This article discusses the relationship between indigenous tourism, crisis situations and resilience from a theoretical and methodological standpoint. The analysis is based on a research process related to indigenous tourism that was implemented during and in the wake of the COVID-19 pandemic. The process involved theoretical discussion of the relationship between tourism, crises and resilience in indigenous peoples as well as the development of innovative methodologies for collaborative work in conditions of confinement for health reasons and openness of the territories. The work was undertaken in the understanding that indigenous tourism is considered a particular type of tourism in which indigenous individuals, families, organizations and communities exercise control and offer an opportunity for encounters. At the same time, however, it has been seen to be a political proposal put forward by indigenous peoples themselves to strengthen their culture and organization. Historically, indigenous peoples have deployed their own strategies in ‘crisis’ situations. Based on this research and the experience of indigenous tourism in Chile, the article discusses, analyses and links these three concepts from a theoretical standpoint before concluding with a methodological proposal.
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    Three-Dimensional Domain Swapping Changes the Folding Mechanism of the Forkhead Domain of FoxP1
    (2016) Medina, Exequiel; Córdova, Cristóbal; Villalobos, Pablo; Reyes, Javiera; Komives, Elizabeth A.; Ramirez Sarmiento, Cesar Antonio; Jorge Babul
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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.