دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Human FoxP Transcription Factors as Tractable Models of the Evolution and Functional Outcomes of Three-Dimensional Domain Swapping
المؤلفون: Pablo Villalobos, César A. Ramírez-Sarmiento, Jorge Babul, Exequiel Medina
المصدر: International Journal of Molecular Sciences; Volume 22; Issue 19; Pages: 10296
بيانات النشر: Multidisciplinary Digital Publishing Institute
سنة النشر: 2021
المجموعة: MDPI Open Access Publishing
مصطلحات موضوعية: domain swapping, protein flexibility, FoxP subfamily, protein evolution, local unfolding, high-resolution biophysics
جغرافية الموضوع: agris
الوصف: 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.
نوع الوثيقة: text
وصف الملف: application/pdf
اللغة: English
العلاقة: Molecular Biology; https://dx.doi.org/10.3390/ijms221910296Test
DOI: 10.3390/ijms221910296
الإتاحة: https://doi.org/10.3390/ijms221910296Test
حقوق: https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.D61E241C
قاعدة البيانات: BASE