ABSTRACT
Protein folding has two meanings--the three-dimensional structure, and the process of forming three-dimensional structure. Simple arguments show that modular assembly is very much faster than sequential assembly. Further, if folding does occur independently in a domain, the condition of chain continuity appears to further favor rapid assembly. This chapter summarizes the evidence that fragments of several other proteins are capable of folding to form native-like structures. These include penicillinase, tryptophan synthetase a-subunits and ß-subunits, and elastase. It shows that protein structural stability is an asset only when employed in moderation, and that native proteins are probably not in their thermodynamically most stable structures. Substantial evidence has accumulated from studies of the folding protein fragments to support this view. Although direct evidence is limited, it appears reasonable to identify folding modules with structural domains.
