Mapping molecular binding by means of conformational dynamics measurements
Year: 2018
Journal: RSC Adv., Volume 8, page 867–876
Authors: do Nascimento, Noelle M.; Juste-Dolz, Augusto; Bueno, Paulo R.; Monzo, Isidro; Tejero, Roberto; Lopez-Paz, Jose L.; Maquieira, Angel; Morais, Sergi; Gimenez-Romero, David
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 TRIM21 alpha 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.
