의생명시스템학부

내용:

Molecular chaperones are ATP-consuming molecular machines that have evolved to assist the folding of biomolecules, thus avoiding the deleterious consequences of misfolding. Thus, it is expected that increasing chaperone concentrations should enhance the yield of native states. While this has been observed in GroEL-mediated protein folding, recent experiments on the folding of ribozyme (RNA enzyme) assisted by CYT-19 show the opposite trend. Here, we reconcile these divergent experimental observations by developing a unified model of chaperone-assisted protein and RNA folding. We show that these ATP-fueled machines drive their substrates out of equilibrium, maximizing the nonequilibrium native yield in a given time rather than the absolute yield or folding rate. We also extend our analysis to explore the role of CYT-19 on the RNA metabolism where the dynamics of molecular degradation and self-splicing interfere with the chaperone-mediated dynamics of ribozyme. When chaperones are reactive to the native state, the self-splicing activity of ribozyme depends non-monotonically on the chaperone activity determined by the CYT-19 and ATP concentrations. Our study shows that the self-splicing yield of ribozyme is maximized under cellular concentrations of CYT-19 and ATP.