Protein Folding and Protein Association

The biosynthesis of proteins leads to linear chain molecules with a well‐defined amino acid sequence that is unambiguously determined by a corresponding polynucleotide sequence at the level of the gene. The underlying mechanism of transcription and translation is based upon the complementarity of pyrimidine and purine bases, on the one hand, and the genetic code, on the other. As indicated by denaturation/renaturation experiments, the one‐dimensional structural information encoded in the polypeptide chain generates a unique three‐dimensional structure. In consequence, one would expect a “folding code” to exist which governs the spontaneous acquisition of the thermodynamically stable “native” structure of a given protein. The rate of folding (in vivo as well as in vitro) is fast, despite the astronomically high number of potential conformations. The mechanism of folding must therefore be kinetically controlled. Whether the native structure represents the “global” or a “local” minimum on the energy hyperspace is an open question. Above a critical size, protein molecules tend to be organized as assemblies made up of identical or non‐identical subunits. The observed uniformity of a given “quaternary structure” requires a close correlation of folding and association as well as a high specificity of subunit recognition. Both are corroborated by in vitro reconstitution experiments.