Principles of Protein Structure - G. Schultz 1982

Covalent Protein Structure
Disulfide Bonds

Most Disulfide Bonds in vitro form spontaneously. As already mentioned, disulfide bridges between pairs of Cysteine residues can link different regions of a protein, resulting in covalently bonded chains. Disulfide bonds also occur in single polypeptide chains. A cysteine residue in a polypeptide chain can only link with a specific, predetermined cysteine residue; therefore, the set of disulfide bridges is strictly unique to a given protein [94–100]. Furthermore, as a rule, these bonds form spontaneously in vitro without requiring external interventions such as Enzymes [94]. Certain known exceptions, such as the disulfide bonds of Insulin and Chymotrypsin [101], are discussed in Section 8.2.

* It might be argued that this advantage is minor, since incorporating a single defective subunit into a tetrameric protein can suppress the function of the entire oligomer. However, this does not usually happen; Oligomeric Proteins exist in a Dynamic State of dissociation and reassociation, whereby subunits are exchanged between oligomers and defective ones are eliminated. Through such disproportionation, natural defects and chemical flaws in individual subunits can be corrected [81].

Immunoglobulin A appeared to be a genuine exception, requiring the J chain for The formation of certain disulfide bonds; however, the J chain can hardly be regarded as an external factor [102].

In vivo, S—S bridges form under reducing conditions. Although cysteine residues are readily oxidized in vitro to cystine residues, it remains unclear how disulfide-containing proteins are formed in vivo and when they emerged during Introduction/18.html">Protein Evolution. These two problems are interrelated. It is hypothesized that the precursors of modern proteins evolved in a reducing atmosphere; in extant Cells, a reducing environment is maintained by the Glutathione system (5 mM reduced glutathione and 0.1 mM oxidized glutathione). Under such conditions, the formation of disulfide bridges in proteins may not occur spontaneously. Therefore, it has been suggested [103] that a system comprising oxidized cystamine and a membrane-bound enzyme could facilitate the introduction of S—S bonds into proteins. These enzymes naturally differ from protein disulfide isomerase [104–107], which rearranges existing disulfide bonds in proteins to yield (meta)stable structures.

The general function of disulfide bonds is to increase the stability of folded proteins (see Section 8.4 and refs [94] and [108]). It is therefore unsurprising that the disruption of certain S—S bridges does not impair protein function (Table 4.1). For instance, in the case of a-amylase, all three disulfide linkages can be reduced without any loss of enzymatic activity [109]. Nevertheless, numerous Examples are known where disulfide bonds serve highly specific Functions.

Class="center">Table 4.1 Reduction of disulfide bridges