Protein Folding: Local Structures, Domains and Assemblies

Summary

Globular proteins show the intrinsic property of acquiring their spatial structure in an autonomous way, based solely on their amino-acid sequence and their aqueous or non-aqueous environment. In order to gain insight into the mechanism of folding the essential steps in the “hierarchical condensation” from the nascent (unfolded) to the native state of a given protein have to be characterized. As taken from spectral data, short-range interactions stabilize well-defined local structures (α-helices, β-turns, loops) in independent segments of the polypeptide chain. In proceeding from elements of secondary- and supersecondary structure to subdomains and domains, the native tertiary and quaternary structure are finally generated by the merging and docking of domains and subunits. Reconstitution after preceding denaturation allows the mechanism of folding to be unravelled; at the same time, it allows “authentic” (native) protein to be recovered from “inclusion bodies”.