The in vitro refolding of hen egg-white lysozyme
is studied in the presence of various osmolytes. Proline
is found to prevent aggregation during protein refolding.
However, other osmolytes used in this study fail to exhibit
a similar property. Experimental evidence suggests that
proline inhibits protein aggregation by binding to folding
intermediate(s) and trapping the folding intermediate(s)
into enzymatically inactive, “aggregation-insensitive”
state(s). However, elimination of proline from the refolded
protein mixture results in significant recovery of the
bacteriolytic activity. At higher concentrations (>1.5
M), proline is shown to form loose, higher-order molecular
aggregate(s). The supramolecular assembly of proline is
found to possess an amphipathic character. Formation of
higher-order aggregates is believed to be crucial for proline
to function as a protein folding aid. In addition to its
role in osmoregulation under water stress conditions, the
results of this study hint at the possibility of proline
behaving as a protein folding chaperone.