PROTEIN-FOLDING

In a cell, as in in vitro, the final conformation of a protein is dete rmined by its amino-acid sequence. The detailed mechanism of polypepti de chain synthesis is well established, but it remains to decipher the second half of the genetic code, which ensures that these chains atta in their functional conformations. The main concepts concerning protei n folding have been developed from in vitro refolding studies. They st ate that the folding of a polypeptide chain is a spontaneous process d epending only on the amino-acid sequence in a given environment. It is thermodynamically controlled and driven by the hydrophobic effect. Co nsequently it was generally accepted that the in vitro process of refo lding adequately reflects the molecular events involved during the in vivo folding of a nascent polypeptide chain. The discovery of molecula r chaperones has led to a re-evaluation of this last point. The possib le mechanisms of unfolding and refolding processes are discussed here in the light of the data available in the literature.