Protein folding and assembly in the endoplasmic reticulum.

The newly synthesized protein emerging through the ER membrane enters a unique environment for folding and assembly. Unlike the cytosol, the ER provides an oxidizing environment, has high levels of calcium, and contains enzymes for N-linked glycosylation. The growing nascent polypeptide chain is in many cases modified co-translationally with N-linked sugars and begins to fold while still attached to the ribosome. Disulfide bond formation stabilizes the tertiary structure of the protein. The in vivo folding and assembly of nascent proteins requires a delicate balance between allowing folding to occur and preventing incorrect interactions that would ultimately lead to improper folding and/or aggregation. In the past several years, two groups of proteins that interact transiently with incompletely folded and assembled proteins in the ER have been identified and characterized. The first group consists of enzymes that promote or stabilize protein folding. The second is composed of proteins termed "molecular chaperones" that bind transiently to nascent polypeptides and apparently prevent misfolding by masking those regions that could lead to incorrect interactions between protein domains or aggregation.