QUESTIONS: alpha-helix "signals" in proteins

murphy kenneth p kpmurphy at blue.weeg.uiowa.edu
Fri Jul 8 09:34:38 EST 1994

In article <2vivmp$qvh at lyra.csx.cam.ac.uk>,
Simon Brocklehurst (Bioc) <smb18 at mole.bio.cam.ac.uk> wrote:

<major deletions>

>  So you could imagine that proteins could fold unproductively if
>they go through the wrong transition state.
>  This does seem to happen in real life.  Ever tried to overexpress a 
>protein in a system that expresses really quickly?  Often the
>protein doesn't fold to it's usual native state.  It's gone along
>some "incorrect" folding pathway from which there's no return.  Express 
>the protein more slowly and the protein folds properly.

I think this is getting well off the path :) of the discussion.  There are alot
of in vivo considerations in this example.  Are you saying that an aggre-
gation of unfolded or partially folded states represents "incorrect" folding?
This is certainly true, but what does it tell us about whether the native fold
is a global minimum?

The Levinthal paradox clearly shows that if the native state is a global mini-
mum, then it isn't obtained through a global search.  This indicates that the 
pathway must be important in some sense.  On the other hand, work by Privalov
has shown that the thermally and urea denatured states are thermodynamically
equivalent and, since you can obtain the native state either by cooling the 
thermally denatured protein or by diluting out the denaturant in the urea den-
atured protein, the folding is independent of path in these cases.

Dr. Kenneth P. Murphy				e-mail: k-murphy at uiowa.edu
Department of Biochemistry			office: (319)335-8910
Univeristy of Iowa				lab:  (319)335-7936
Iowa City, IA 52242            		        FAX:  (319)335-9570

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