β(2)-microglobulin forms 3D domain-swapped amyloid fibrils with disulfide linkages

β(2)-microglobulin (β(2)m) is the light chain of type I major histocompatibility complex. It deposits as amyloid fibrils within joints during long-term hemodialysis treatment. Despite the devastating effects of dialysis-related amyloidosis, full understanding of how fibrils form from soluble β(2)m remains elusive. Here we show that β(2)m can oligomerize and fibrillize via 3D domain swapping. Isolating a covalently bound, domain-swapped dimer from β(2)m oligomers on the pathway to fibrils, we were able to determine its crystal structure. The hinge loop which connects the swapped domain to the core domain includes the fibrillizing segment LSFSKD, whose atomic structure we also determined. The LSFSKD structure reveals a Class 5 steric zipper, akin to other amyloid spines. The structures of the dimer and the zipper spine fit well into an atomic model for this fibrillar form of β(2)m, which assembles slowly under physiological conditions.