Role of cofactors in protein folding.

Although cofactors are essential components of many proteins to attain biological activity, the role of cofactors in protein folding is not well understood. Biophysical characterization of four types of cofactor-binding proteins (with copper, flavin moiety, iron-sulfur cluster, and heme cofactors, respectively) provides the following insights. (1) The presence of the cofactor often stabilizes the native protein. (2) The cofactor has the ability to interact specifically with the unfolded polypeptide. (3) The presence of the cofactor is sometimes essential for the polypeptide to fold. (4) Coordination of the cofactor prior to polypeptide folding can dramatically accelerate formation of the functional protein.