disulphide bonds in nuclear proteins

kresten kresten at my-deja.com
Tue Feb 20 07:08:55 EST 2001

"Frank Fuerst" <ffrank at rz.uni-potsdam.de> wrote in message
news:96rcj7$mjhpq$1 at fu-berlin.de...
> Lyndsay_Smith at xenova.co.uk (Lyndsay Smith) wrote:
> >Hi
> >
> >I'm interested in some information on disulphide bond formation in
> >I've read that disulphide bonds are more stable in extracellular proteins
> >than in cytosolic proteins.
> I doubt this, or at least I would put it otherwise. The cellular
> environment is quite reducing in the cytosol, while it is more
> oxidizing in the ER, periplasm etc. Thus, cytosolic proteins usually
> don't have any disulfide bridges in their native structure, whereas
> secreted proteins often have.

Look up OxyR, which I think is a redox regulated (dithiol = disulfide)
transcription factor or Hsp33 which is redox regulated chaperone.

> >My query is are disulphide bonds stable in
> >nuclear proteins?
> I don't know, but it should be possible to look up the redox state of
> the nucleus if you know the right book.

This is the major problem! There is yet no good method published for
determining redox-potentials (dithiol = disulfide) in vivo. The common
"known" fact that the ER is much more oxidizing than the cytoplasm is as far
as I know it mostly based on one paper:
Hwang C, Sinskey AJ, Lodish HF.
Oxidized redox state of glutathione in the endoplasmic reticulum.
Science. 1992 Sep 11;257(5076):1496-502.

Whenever somebody comes up with a good non-perturbing method for determining
redox potentials in vivo, it will be more resonable to take this discussion

> Unfortunately, recent investigations have shown that the
> GSH/GSSG-ratio (glutathion), which is usually used to quantify if a
> cellular compartment is reducing or oxidizing, is not the redox agent
> acting on proteins. In eucaryotes, disulfide bond formation is
> mediated by PDI in the ER. Tu et al. (Science 290 (2000), p. 1571-74)
> have shown that PDI is re-oxidized by the protein Ero1p (in yeast)
> which in turn is re-oxidized by soluble FAD. It seems that the
> FAD_red/FAD_ox-ratio is kinetically decoupled from the GSH/GSSG-ratio,
> so the latter is not a good measure when talking about eucaryotic
> disulfide bond formation.

Yup. I completely agree that kinetics is very important here. In fact it may
prove irrelevant to speak of a redox-potential, since thermodynamics may be
much less important than kinetics.


> Regards, Frank

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