The functions of many proteins critically depend on the proper folding of the polypeptide chain. Some proteins spontaneously fold into their correct shapes, but for others, correct folding may initially require the participation of other molecules called molecular chaperones.

After translation, proteins in both prokaryotic and eukaryotic cells may undergo alterations termed posttranslational modifications. A number of different types of modifications are possible. Some proteins are synthesized as larger precursor proteins and must be cleaved and trimmed by enzymes before the proteins can become functional. For others, the attachment of carbohydrates may be required for activation. Amino acids within a protein may be modified: phosphates, carboxyl groups, and methyl groups are added to some amino acids. In eukaryotic cells, the amino end of a protein is often acetylated after translation.