Human FoxP Transcription Factors as Tractable Models of the Evolution and Functional Outcomes of Three-Dimensional Domain Swapping

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dc.contributor.authorVillalobos, Pablo
dc.contributor.authorRamirez Sarmiento, Cesar A.
dc.contributor.authorBabul, Jorge
dc.contributor.authorMedina, Exequiel
dc.date.accessioned2025-05-01T10:30:21Z
dc.date.available2025-05-01T10:30:21Z
dc.date.issued2021
dc.description.abstractThe 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.
dc.description.funderANID
dc.description.funderFONDECYT
dc.format.extent14 páginas
dc.fuente.origenWOS
dc.identifier.doi10.3390/ijms221910296
dc.identifier.eissn1422-0067
dc.identifier.issn2175-3369
dc.identifier.pubmedidMEDLINE:34638644
dc.identifier.scieloidS0718-69242020000300109
dc.identifier.scopusidSCOPUS_ID:65649135122
dc.identifier.urihttps://doi.org/10.3390/ijms221910296
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/103623
dc.identifier.wosidWOS:000756225000001
dc.information.autorucInstituto de Ingeniería Biológica y Médica; Ramirez Sarmiento Cesar Antonio; 0000-0003-4647-903X; 1037905
dc.issue.numero19
dc.language.isoen
dc.nota.accesoSin adjunto
dc.pagina.final16
dc.pagina.inicio4
dc.relation.ispartof16th International Vasculitis & ANCA Workshop
dc.revistaINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
dc.rightsregistro bibliográfico
dc.subjectdomain swapping
dc.subjectprotein flexibility
dc.subjectFoxP subfamily
dc.subjectprotein evolution
dc.subjectlocal unfolding
dc.subjecthigh-resolution biophysics
dc.subjectDNA-BINDING
dc.subjectFORKHEAD DOMAIN
dc.subjectCRYSTAL-STRUCTURE
dc.subjectGENE FAMILY
dc.subjectHINGE LOOP
dc.subjectPROTEIN
dc.subjectDYNAMICS
dc.subjectMECHANISM
dc.subjectCOMPLEX
dc.subjectMULTIDOMAIN
dc.subject.ddc400
dc.subject.deweyLenguases_ES
dc.subject.ods11 Sustainable cities and communities
dc.subject.odspa11 Ciudades y comunidades sostenibles
dc.titleHuman FoxP Transcription Factors as Tractable Models of the Evolution and Functional Outcomes of Three-Dimensional Domain Swapping
dc.typeartículo
dc.volumen22
sipa.codpersvinculados1037905
sipa.indexWOS
sipa.trazabilidadCarga WOS-SCOPUS;01-05-2025
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