Intrinsic disorder and salt-dependent conformational changes of the N-terminal region of TFIP11 splicing factor

Blinera Juniku, Julien Mignon, Rachel Carême, Alexia Genco, Anna Maria Obeid, Denis Mottet, Antonio Monari, Catherine Michaux

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs

Résumé

Tuftelin Interacting Protein 11 (TFIP11) was identified as a critical human spliceosome assembly regulator, interacting with multiple proteins and localising in membrane-less organelles. However, a lack of structural information on TFIP11 limits the rationalisation of its biological role. TFIP11 is predicted as an intrinsically disordered protein (IDP), and more specifically concerning its N-terminal (N-TER) region. IDPs lack a defined tertiary structure, existing as a dynamic conformational ensemble, favouring protein-protein and protein-RNA interactions. IDPs are involved in liquid-liquid phase separation (LLPS), driving the formation of subnuclear compartments. Combining disorder prediction, molecular dynamics, and spectroscopy methods, this contribution shows the first evidence TFIP11 N-TER is a polyampholytic IDP, exhibiting a structural duality with the coexistence of ordered and disordered assemblies, depending on the ionic strength. Increasing the salt concentration enhances the protein conformational flexibility, presenting a more globule-like shape, and a fuzzier unstructured arrangement that could favour LLPS and protein-RNA interaction. The most charged and hydrophilic regions are the most impacted, including the G-Patch domain essential to TFIP11 function. This study gives a better understanding of the salt-dependent conformational behaviour of the N-TER TFIP11, supporting the hypothesis of the formation of different types of protein assembly, in line with its multiple biological roles.

langue originaleAnglais
Numéro d'article134291
journalInternational journal of biological macromolecules
Volume277
Numéro de publication3
Les DOIs
Etat de la publicationPublié - oct. 2024

Empreinte digitale

Examiner les sujets de recherche de « Intrinsic disorder and salt-dependent conformational changes of the N-terminal region of TFIP11 splicing factor ». Ensemble, ils forment une empreinte digitale unique.
  • CÉCI – Consortium des Équipements de Calcul Intensif

    CHAMPAGNE, B. (Responsable du Projet), Lazzaroni, R. (Responsable du Projet), Geuzaine , C. (Co-investigateur), Chatelain, P. (Co-investigateur) & Knaepen, B. (Co-investigateur)

    1/01/1831/12/22

    Projet: Recherche

Contient cette citation