This very interesting fundamental discussion is a little bit
disguised by the rather more specific subject title...
Regarding thermodynamic versus kinetic control of protein
folding, I would like to mention the case of some serpin
protein inhibitors, in particular plasminogen activator
inhibitor, studied by E. Goldsmith and co-workers.
PAI has an inhibitory fold in vitro only for
a limited time, and then undergoes a transition to a latent
state (see Mottonen et al., Nature 355, 270-273, 1992; see
also a recent issue of Structure for related
serpin work and discussion).
In vivo, the active form may be stabilized by complexation.
The point is, the primary functional conformation is NOT
the global minimum for the isolated protein. Is this
kinetic control? Even if the complexed form in vivo IS
a global minimum (and I don't know what the current opinion
on this is), is it a case where a metastable fold has to be
'captured' and complexed.
Any serpin researchers reading this who could comment?
-R.Engh
