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