General review on the oxidative folding of small disulfide-rich proteins are available
[Arolas et al, 2006;
The Knottin PCI folds in a complex process
The folding pathway of the Potato Carboxypeptidase A Inhibitor
PCI has been analyzed by structural analysis and stop/go folding
et al., 1994].
Folding of PCI proceeds through an initial stage of nonspecific
1- and 2- and 3-disulfide intermediates are highly heterogeneous.
Disulfide reshuffling occurs at the final stage which
refines and consolidates the scrambled species to acquire the
Comparison with other small disulfide-rich proteins show that
proteins such as PCI with their native disulfide bonds reduced
in a collective and simultaneous manner exhibit both a high degree
of heterogeneity of folding intermediates and the accumulation
of scrambled isomers along the folding pathway [Chang
& Bulychev, 2000a].
Analysis of the unfolding pathway of PCI has revealed the
existence of structurally defined unfolding intermediates
[Chang et al., 2000b].
It was also shown that the PCI sequence is unable to fold
quantitatively into a single native structure, and that,
under physiological conditions, the scrambled isomers of PCI
that constitute about 4% of the protein are in equilibrium with
PCI folding does not depend on the prosequence
Folding of the Potato Carboxypeptidase A Inhibitor PCI has
been studied with or without the prosequences, either in vitro
or in vivo in Escherichia coli [Bronsoms
et al., 2003].
It is shown that the prosequence does not affect folding significantly
neither in vitro nor in vivo.