> 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. 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
