INCLUSION-BODY FORMATION BY INTERLEUKIN-1-BETA DEPENDS ON THE THERMALSENSITIVITY OF A FOLDING INTERMEDIATE

We show that sequence and growth temperature effects on IB formation i n the small, monomeric beta-barrel protein interleukin-1 beta (IL-1 be ta) can be quantitatively reproduced in an in vitro system in which IL -1 beta is refolded from denaturant at different temperatures. The res ults suggest that temperature and mutational effects on IB formation m ay be based on intrinsic properties of the protein sequence rather tha n interactions with chaperones or other cellular factors. We also repo rt striking correlations of IB formation with mutation-dependent chang es in residue hydrophobicity. The nature of these trends differs consi derably with residue position, however, suggesting that they are media ted by particular local environments created by an ordered structure.