Retardation of folding as a possible means of suppression of a mutation in the leader sequence of an exported protein.

We have proposed (Randall, L. L., and Hardy, S. J. S. (1986) Cell 46, 921-928) that during export of protein from Escherichia coli, there is a kinetic partitioning between the pathway that leads to productive translocation and the pathway that leads to folding of precursors into a stable conformation that is incompatible with export. This model predicts that a decrease in rate along the productive pathway resulting from a defect in the leader sequence could be partially overcome by slowing the folding of the precursor and thereby increasing the time during which that polypeptide would be competent to enter the export pathway. Here it is shown that a change in the mature portion of maltose-binding protein that is known to suppress a mutation in the leader sequence (Cover, W. H., Ryan, J. P., Bassford, P. J., Jr., Walsh, K. A., Bollinger, J., and Randall, L. L. (1987) J. Bacteriol. 169, 1794-1800) also decreases the rate of folding of the precursor.