Mapping molecular binding by means of conformational dynamics measurements
| Autor: | Augusto Juste-Dolz, Paulo Roberto Bueno, Isidro S. Monzó, Sergi Morais, Ángel Maquieira, David Giménez-Romero, José Luis López-Paz, Roberto Tejero, Noelle M. do Nascimento |
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| Přispěvatelé: | Universitat Politècnica de València Camino de Vera, Universidade Estadual Paulista (Unesp), Universitat de València |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Physics Drug discovery Mechanism (biology) General Chemical Engineering Dynamics (mechanics) Molecular binding General Chemistry Quartz crystal microbalance 03 medical and health sciences 030104 developmental biology Dual-polarization interferometry QUIMICA ANALITICA Biological system |
| Zdroj: | RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia instname Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 2046-2069 |
| Popis: | [EN] Protein-protein interactions are key in virtually all biological processes. The study of these interactions and the interfaces that mediate them play a key role in the understanding of biological function. In particular, the observation of protein¿protein interactions in their dynamic environment is technically difficult. Here two surface analysis techniques, dual polarization interferometry and quartz crystal microbalance with dissipation monitoring, were paired for real-time mapping of the conformational dynamics of protein¿ protein interactions. Our approach monitors this dynamics in real time and in situ, which is a great advancement within technological platforms for drug discovery. Results agree with the experimental observations of the interaction between the TRIM21a protein and circulating autoantibodies via a bridging bipolar mechanism. This work provides a new chip-based method to monitor conformational dynamics of protein¿protein interactions, which is amenable to miniaturized high-throughput determination. Financial support from the Generalitat Valenciana (GVA-PROMETEO/2014/040), the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (CTQ2013-45875-R and CTQ2013-42914-R) is acknowledged. |
| Databáze: | OpenAIRE |
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