On Monday, June 18, 2012 02:06:46 pm Alexander Scouras wrote:
> > I'm further racking my brain to figure out a biological implication of this
> > behaviour, I thought something like plaque formation but I can't find
> > support in literature.
>
>
> There are a variety of domain swapped crystal structures out there, but at
> least the two I'm most familiar with are regarded as being crystallization
> artifacts. I think I recall seeing examples where domain swapping was
> biologically relevant, but my impression is most are red herrings.
You might be interested in the following paper, which describes
domain-swapped ("domain exchange") dimerization as a control mechanism for
kinases.
Activation segment dimerization: a mechanism for kinase
autophosphorylation of non-consensus sites.
Pike, A.C.W., Rellos, P., Niesen, F.H., Turnbull, A., Oliver, A.W.,
Parker, S.A., Turk, B.E., Pearl, L.H., Knapp, S.,
Journal: (2008) Embo J. 27: 704
But these are specifically dimeric. Unlike the case posted here,
there is not a second non-swapped interface that would allow
formation of an infinite chain.
Ethan
>
> In the poster child of plaque formation, prion protein formed cys-cross
> linked domain swapped dimers in some crystals.
>
> http://www.nature.com/nsmb/journal/v8/n9/abs/nsb0901-770.html
>
> However, using PAGE & DLS it was later shown that prion has no preference for
> dimers when you break down Infectious fibrils. Cross linked dimers definitely
> out. Any subunits ruled out, in fact.
>
> http://www.nature.com/nature/journal/v437/n7056/abs/nature03989.html
>
>
> RNaseA is another example, and isn't even a disease associated molecule.
> Similarly to how we've found that many/most proteins may be converted to
> amyloid forms by harsh enough conditions, I think some will domain swap, and
> some authors have pursued domain swapping heavily with RNaseA a as a "model
> for amyloid formation". RNaseA will swap in major and minor conformations
> even, though not in the same crystal. Still, that's the first thing you need
> for an infinite series, is two compatible/simultaneous swapping points.
>
>
> Now, I do think domain swapping, particularly an infinite chain, can be
> interesting from a bioengineering or biophysical level, if that is what you
> are interested in. I just want to say that there is a high bar to showing
> biochemical relevance in the sense of holding any physiological implications.
>
>
> Alexander D. Scouras
> Postdoctoral Fellow
> Alber Lab, QB3
> University of California, Berkeley
--
Ethan A Merritt
Biomolecular Structure Center, K-428 Health Sciences Bldg
University of Washington, Seattle 98195-7742
