Mitraki, A. and King, J. (1989) Bio/technology, 7, 690-697

Protein folding intermediates and inclusion body formation


The accumulation of newly synthesized polypeptide chains expressed from cloned genes as non native aggregates has become an important factor in the recovery of such proteins. Studies of both the refolding of denatured proteins in vitro, and of in vivo folding and maturation pathways, indicate that aggregates derive from specific partially folded intermediates and not from mature native, or fully unfolded proteins. The aggregation process in both homologous and heterologous cytoplasms may be driven by partial intracellular denaturation of intermediates, for example by high temperature, or by the absence of a critical factor - prosthetic group, subunit, chaperone - during the maturation process. All of these processes appear to be highly specific and subject to modification by genetic engineering of the intermediates, or alteration of their environment. This requires appreciation of the properties of such intermediates as distinct from the native states.

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