Proteins fold under mechanical forces in a number of biological processes, ranging from muscle contraction to co-translational folding at the mouth of the ribosome. As force hinders the folding reaction, chaperones must play a crucial role in this scenario. Nevertheless, to date, it has not been possible to monitor the direct influence of a chaperone on a protein folding under force. Here, we introduce single molecule magnetic tweezers to study the folding dynamics of protein L in presence of the prototypical molecular chaperone Trigger Factor (TF) over the range of physiological forces (4 to 10 pN). Our results show that TF modulates the folding of protein L by prominently increasing the probability of folding against the force and accelerating the refolding kinetics. Moreover, we find that the ability of TF to catalyze the folding reaction depends on the pulling force; as the force increases, higher concentrations of TF are needed for rescue folding, although no effect is observed above 12 pN even with saturating amounts of TF. Here, we propose for the first time that chaperones such as TF can work as foldases under force, playing a relevant role in many biological processes such as protein translation.
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