| Popis: |
A fundamental question in protein folding is whether proteins fold through one or multiple trajectories. Although most protein folding experiments indicate a single pathway, we have demonstrated the presence of multiple unfolding pathways in a simple, two-state folding protein using a combination of chemical denaturant, mechanical force and site-directed mutations. This raises the question of how environmental conditions affect the folding mechanism. We find that under most conditions a single pathway is dominant, but seemingly small changes in force, denaturant concentration and protein sequence can strongly modulate the flux between the pathways. This result suggests that in vivo, the heterogeneous crowded cellular environment could strongly influence the mechanisms of protein folding and unfolding. Another perturbant that could affect the folding pathway in vivo is the ribosome since many proteins fold while they are being translated. Comparison of the pathway in experiments on and off the ribosome will reveal how the ribosome affects the folding mechanism. |
