Glimpses of the molecular mechanisms of β(2)-microglobulin fibril formation in vitro: Aggregation on a complex energy landscape

β(2)-microglobulin (β(2)m) is a 99-residue protein that aggregates to form amyloid fibrils in dialysis-related amyloidosis. The protein provides a powerful model for exploration of the structural molecular mechanisms of fibril formation from a full-length protein in vitro. Fibrils have been assembled from β(2)m under both low pH conditions, where the precursor is disordered, and at neutral pH where the protein is initially natively folded. Here we discuss the roles of sequence and structure in amyloid formation, the current understanding of the structural mechanisms of the early stages of aggregation of β(2)m at both low and neutral pH, and the common and distinct features of these assembly pathways.