> > 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. >
A good example of domain swaps involved in disease-associated polymerisation is the polymerisation of serpins; while there is still some debate about whether this mechanism is actually what happens in patients in vivo, the formation of polymers via domain swapping is becoming widely accepted as the new paradigm. Relevant references include: Nature. 2008 Oct 30;455(7217):1255-8. Epub 2008 Oct 15. Crystal structure of a stable dimer reveals the molecular basis of serpin polymerization. Yamasaki M, Li W, Johnson DJ, Huntington JA. PMID: 18923394 EMBO Rep. 2011 Sep 30;12(10):1011-7. doi: 10.1038/embor.2011.171. Molecular basis of α1-antitrypsin deficiency revealed by the structure of a domain-swapped trimer. Yamasaki M, Sendall TJ, Pearce MC, Whisstock JC, Huntington JA. PMID: 21909074 Interestingly enough they don't rely on disulfide formation ("normal" polymers fall apart on an SDS gel but not a native gel), but they can be engineered to include disulfides which render the polymers stable to SDS (on a non-reducing gel). This was actually a really useful tool in determining exactly which domains of a given molecule swapped into their neighbour during polymerisation. Best Regards Tom