Oxidative folding

This is made possible by a 21 kDa inner membrane protein, called DsbB, which has two pairs of cysteine residues.

Eventually, this cross-link between the two proteins is broken by a nucleophilic attack of the second cystein residue in the DsbA active site.

On his turn, DsbB is reoxidized by transferring electrons to oxidized ubiquinone, which passes them to cytochrome oxidases, which finally reduce oxygen; this is in aerobic conditions.

As molecular oxygen serves as the terminal electron acceptor in aerobic conditions, oxidative folding is conveniently coupled to it through the respiratory chain.

Next, the attack of a second cysteine residue results in the forming of a more stable disulfide in the refolded protein.

Because these two pathways coexist next to each other in the same periplasmic compartment, there must be a mechanism to prevent oxidation of DsbC by DsbB.

A second difference is that in eukaryotes, the use of molecular oxygen as a terminal electron acceptor is not linked to the process of oxidative folding through the respiratory chain as is the case in bacteria.

In fact, one of the proteins involved in the oxidative folding process uses a flavin-dependent reaction to pass electrons directly to molecular oxygen.

There, the reduction of molecular oxygen to water is carried out by a complex series of proteins, which catalyse this reaction very efficiently.

In eukaryotes, the respiratory chain is separated from oxidative folding since cellular respiration takes place in the mitochondria and the formation of disulfide bonds occurs in the ER.

Classical examples of proteins in which the process of oxidative folding is well studied are bovine pancreatic trypsin inhibitor (BPTI) and ribonuclease A (RNaseA).