Host: Lu Wang
"Structural and Dynamic NMR Studies of Integrin-Collagen Interactions"
The binding of integrin receptors to collagen mediates cell-extracellular matrix adhesion processes and its dysregulation plays critical roles in arthritis, cancer and heart disease. Collagen is a long rod-like shaped ligand, and its mechanism of recognition and role in selectivity and affinity are unique, and at this stage not well understood. Using NMR together with other biophysical techniques, we have developed a novel picture of the integrin αI binding to collagen and have shown that dynamics plays a central role in the binding. NMR is a particularly powerful tool for studying dynamics over a wide range of timescales and 15N relaxation dispersion experiments, along with hydrogen-deuterium exchange (HDX) experiments, have highlighted that αI affinity and selectivity to different collagen motifs may arise from complex dynamics on the μs-ms timescale and the slower HDX timescales.