Beta-2 microglobulin (beta 2m) is the light chain of class I major histocompatibility complex (MHC-1). beta 2m is an intrinsically amyloidogenic protein that can assemble into amyloid fibrils in a concentration dependent manner. beta 2m is accumulated in serum of haemodialysed patients, and deposited in the skeletal Joints, causing dialysis related amyloidosis. Recent reports Suggested that the loop comprised between beta 2m strands D and E is crucial for protein stability and for beta 2m propensity to aggregate as cross-beta structured fibrils. In particular, the role of Trp60 for beta 2m stability has been highlighted by showing that the Trp60 -> Gly beta 2m mutant is more thermo-stable and less prone to aggregation than the wild type protein. On the contrary the Asp59 -> Pro, beta 2m mutant shows lower Tm and stronger tendency to fibril aggregation. To further analyse such properties, the Trp60 -> Val beta 2m mutant has been expressed and purified; the propensity to fibrillar aggregation and the folding stability have been assessed, and the X-ray crystal structure determined to 1.8 angstrom resolution. The W60V mutant structural features are discussed, focusing oil the roles of the DE loop and of residue 60 in relation to beta 2m structure and its amyloid aggregation trends. (C) 2009 Elsevier Inc. All rights reserved.