Molecular mechanistic insights into the OX40 – OX40L complex from biophysical and computational analyses
Rattachement africain : jp, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
OX40 and OX40L belong to the tumor necrosis factor receptor superfamily (TNFRSF) and tumor necrosis factor superfamily (TNFSF), respectively. Protein-protein interactions between OX40 and OX40L facilitate T cell responses, triggering various immunological and pathophysiological events. Excessive activation frequently contributes to the onset of autoimmune and allergic diseases. Therefore, the OX40/OX40L system is considered a promising target for drug discovery. Given that the structure of the OX40-OX40L complex exhibits some unique features compared to other members of these protein super families, it is reasonable to assume that this tandem possesses distinct interaction mechanisms. However, detailed interaction analysis using quantitative parameters such as binding kinetics or thermodynamics, with remains to be performed for OX40/OX40L. In this study, we identified several hot spot residues from the OX40 cysteine-rich domains (CRDs) 1 to 3 by alanine scanning. Kinetic and thermodynamic analysis combined with molecular dynamics simulations highlighted the characteristics of a hot spot from CRD3 due to its indirect influence on those from CRD1 and CRD2, providing insights into the interaction mechanism and a strategy for drug discovery targeting this interaction.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Molecular mechanistic insights into the <scp>OX40</scp> – <scp>OX40L</scp> complex from biophysical and computational analyses
- Date Crossref
- 27/12/2025
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Kyushu University Department of Protein Drug Discovery pays non établi dans la noticeUniversité ou école supérieure
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Innovative Research (United States) pays non établi dans la noticeEntreprise
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The University of Tokyo Medical Device Development and Regulation Research Center pays non établi dans la noticeUniversité ou école supérieure
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University of Toyama Laboratory of Molecular Cell Biology pays non établi dans la noticeUniversité ou école supérieure
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Laboratory for Materials and Structures Institute of Innovative Research pays non établi dans la noticeStructure de recherche
Department of Protein Drug Discovery — Kyushu University, Innovative Research (United States) et Medical Device Development and Regulation Research Center — The University of Tokyo, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.