Three-dimensional domain swapping and its relevance to conformational diseases

When a protein undergoes oligomerization via three-dimensional (3D) domain swapping, its molecules exchange secondary structure elements recreating the monomeric fold in an aberrant way, i.e., from chain segments belonging to different molecules. There is a hypothetical possibility that if this process took place in an open-ended, rather than reciprocal, fashion it could lead to the formation of pathological amyloid fibrils, which are associated with several conformational disorders. 3D domain swapping and disease-causing amyloid aggregation have been reported for many proteins, but human cystatin C (HCC) and the prion protein (PrP) are the only examples for which both phenomena have been observed.