Quiescin-sulfhydryl oxidases and oxidative protein folding
- Last Updated on 01 April 2013
Our group, in collaboration with Donald Coppock, uncovered a new enzyme family (abbreviated QSOX: Quiescin-sulfhydryl oxidase) that is capable of facile and direct insertion of disulfide bonds into reduced unfolded client proteins. Mispaired disulfide bonds are corrected by isomerization using a second enzyme, protein disulfide isomerase (PDI).
QSOX enzymes are present in most eukaryotes, but they are absent in yeast/fungi. Intracellularly, they are found in the endoplasmic reticulum and the Golgi. In addition, a significant fraction of QSOX appears to be secreted from cells. QSOX immunoreactivity is particularly prominent in cells with a heavy secretory load [see Immunohistochemistry].
QSOXs can contain one or two thioredoxin (Trx) domains as shown:
Next comes a helix-rich domain (HRR), followed by the FAD binding domain (Erv/ALR) originally identified by Fass and coworkers for the yeast Erv2p protein. The flow of reducing equivalents from a protein substrate (arrow 1), through the two redox-active disulfides (CxxC motifs; arrow 2), to the flavin ring (arrow 3) and then to molecular oxygen (arrow 4) is shown here:
We are currently studying representative examples of both one- and two-Trx QSOX enzymes to learn how these proteins are so effective at generating disulfide bonds in unfolded reduced proteins.