ABSTRACT
Mitraki, A., Haase-Pettingell, C., and King J. (1991) In Protein Refolding (G. Georgiou & E. de Bernardez-Clark, eds.) ACS Sympsosium Seris 470, American Chemical Society, Washington, D.C., pp. 35-49
"Mechanisms of inclusion body formation"
The accumulation of newly synthesized polypeptide chains as aggregated inclusion bodies is becoming a serious problem in the recovery of proteins from cloned genes. Studies of both refolding of denatured proteins in vitro and of in vivo folding and maturation pathways, indicate that aggregates derive from partially folded intermediates in the pathway and not from the native protein. Aggregation is not a function of the solubility and stability properties of the native state, but those of folding intermediates in relation to the environment they are folding in. Ions, cofactors and chaperonins can interact with intermediates and influence the outcome of the folding process. Single amino acid substitutions can suppress aggregation without affecting the activity and stability of the mature protein. Thus, it should be possible to optimize folding pathways with genetic engineering of the intermediates, or alteration of the environment.
