Chaperones, Molecular
509
However, proteins have been identifed
in the periplasm oF
E. coli
that catalyze
both the Formation and removal oF disul-
fdebondsandthusspeedupthera
tea
t
which proteins that contain such bonds
are Folded.
The two major proteins in
E. coli
involved
in this process are both periplasmic
proteins and are called DsbA and DsbC
(±ig. 6). DsbA is a powerFul oxidant,
catalyzing the Formation oF disulfde bonds
between cysteine residues in proteins
that have been newly secreted to the
periplasm, and itselF becoming reduced as
aconsequence
.A
l
thoughbac
ter
ialack
ing
DsbA are viable, they show enhanced
turnover oF periplasmic proteins (owing to
the presence oF proteases in the periplasm
that degrade unFolded proteins), lack oF
motility (owing to the Failure oF flagella to
assemble), and high sensitivity to reducing
agents. DsbA apparently binds proteins in
a hydrophobic groove, rather analogous
to the mechanism seen in some oF the
DsbA (ox)
DsbA (red)
DsbB (ox)
DsbB (red)
Periplasm
DsbC (red)
DsbC (ox)
DsbD (ox)
DsbD (red)
Substrate protein
(oxidized)
Substrate protein
(reduced)
Coupled to electron
acceptors via quinones
Reduced by NADPH via
thioredoxin
Cytosol
Fig. 6
Mode of action of some of the periplasmic Dsb proteins in
E. coli
.DsbAactsasan
oxidase to introduce disulFde bonds into proteins with free thiols. In doing this, it is itself
reduced, and must be reoxidized by oxidizedDsbB,whichinturnbecomesreduced.DsbB
becomes reoxidized by donating electrons to quinines, which flow to oxygen or other electron
acceptors. DsbC in its reduced form acts either as a reductase (the net effect of which is to
oxidize DsbC) or an isomerase (where no net redox reaction occurs). In the former capacity, it
must be rereduced before regaining its activity; this is done by DsbD, which in turn derives its
reducing power ultimately from cytosolic NADPH. Other Dsb proteins also exist in the
periplasm of
E. coli
but have been omitted for clarity.
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