QUESTIONS: alpha-helix "signals" in proteins
bjd12 at cus.cam.ac.uk
Tue Jul 5 10:24:53 EST 1994
Ken Prehoda (kenp at nmrfam.wisc.edu) wrote:
: In article <2vbn6u$j4e at usenet.rpi.edu> Mark J. Dresser, writes:
: >QUESTIONS: What role do/could tertiary interactions play in stabilizing
: >the alpha-helix?
: Probably a significant role, but this is only my opinion. There is a
: great deal of work being done on small, helix forming peptides (cf.
: Baldwin and coworkers). But, the question one must ask is whether
: secondary structure is present in the unfolded protein. If it
: is not (which seems to be the case - molten globules and other
: curiosities not withstanding), then this seems good evidence that
: tertiary structure is indeed necessary for secondary structure
I think that more proteins need to be characterised under denaturing
conditions before the question of structure in unfolded proteins can be
answered properly. Certainly in the cases where unfolded proteins have been
characterised (434 repressor, FK506 BP) structures have been found. They
tend to be marginal, rather than persistent, but they do seem to be formed.
This kind of implies that local interactions can form, and so presumably
would form early in a folding reaction.
: >Rose proposes that "the folded structure of a protein is encrypted in
: >aa secquence, written in a *code* that remians obscure". (Rose, G.D. et
: >al. (1994) _Science_ 264, 1126). What is the status of this obscure
: >that he is referring to? Is the existence of this *code* a widely held
: The status of this "code" is abysmal. We know very little about the
: relationship of primary and higher order structures of proteins. The
: existence of such a code is certainly widely held (cf. Anfinsen and
: coworkers). If we believe that all of the information is contained
: in the sequence itself, then it follows that there should be some
: type of code that determines protein structure. But maybe the code
: is different for every protein?
I think that its a fairly safe bet that the structure of a protein is
determined by its sequence, and that its unlikely (and overly pessimistic)
to think that the rules governing this final structure are different for
each sequence. However, it does seem that its complicated, and that there's
no easy answers to the question of the folding pathway, or even the final
fold. I personally suspect that the solution will involve looking for
adoption of structures in a hierachical manner - clusters, local secondary
structures, tertiary structures, and so on.
: Looking forward to further discussion,
Indeed. Could be a good thread.
: Ken Prehoda
: kenp at nmrfam.wisc.edu
MRC Protein Function and Design,
"They can make me do it, but they can't make me do it with dignity."
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