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3743062
Structure and dynamics of HER2 directed Chimeric T-Cell Receptor (CAR) using homology modeling and all-atom molecular dynamics simulation with explicit solvent
Date
August 24, 2022
Chimeric antigen receptor (CAR) is a genetically engineered T-cell receptor that is used in targeted immunotherapy by recognizing antigen and activating immune response against cancer cells. A critical step of activating this pathway is the signal transduction cross the membrane, yet high resolution structure of the full CAR is not available, which hinders our understanding of the receptor activation. In this study, we built a full-length homology model of a HER2 directed CAR. Molecular dynamics (MD) simulation is carried out to probe structure and dynamics of this receptor in its apo form. Our MD data has shown that a). the extra-cellular domain anti-HER2 scFv and the intracellular domains (4-1BB and CD3Z) maintain their stable folders. b). the transmembrane part of the hinge domain maintains helical conformation. C). the extra-and intra-cellular region of the receptor was found to be highly flexible, suggesting possibility of long-ranged signal coupling.
Chimeric antigen receptor (CAR) is a genetically engineered T cell receptor applied in the T-cell therapy, which can be a cure for blood cancer. Currently, there are six FDA approved CARs for such treatment; yet, the CAR-T cell therapy has not been extended to solid tumors…
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