Heparin and β2-microglobulin amyloidogenesis

β2-Microglobulin (β2M) occurs as a precursor protein in dialysis-related amyloidosis (DRA), which is a major complication in lives of patients undergoing dialysis.  However, the underlying mechanism by which a native β2M transform into an amyloid β2M remain unclear.  This disease has developed exclusively in interstitial tissues, which suggest possible implication of extracellular matrix substances in amyloidogenesis of this precursor protein.  By using our monoclonal antibody specific for amyloid β2M, we investigated the function of heparin, that is, one of the glycosaminoglycans, as associated with amyloidogenic conversion of the β2M molecule.  We confirmed that heparin induced a dose-dependent and time-dependent unfolding at the C-terminal region of the β2M molecule, which led to amyloidogenic transformation of the β2M molecule and brought about intermolecular interactions between β2M and substances in the interstitial matrix such as GAGs and collagen.