Quiescin-sulfhydryl oxidases and oxidative protein folding

Published on: Author: Colin Thorpe

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.


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