biostudies-literatureMyers SLWellcome TrustBiotechnology and Biological Sciences Research Council2311-21https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618240biostudies-literatureUnknown45(7)Beta(2)-microglobulin (beta(2)m) forms amyloid fibrils that deposit in the musculo-skeletal system in patients undergoing long-term hemodialysis. How beta(2)m self-assembles in vivo is not understood, since the monomeric wild-type protein is incapable of forming fibrils in isolation in vitro at neutral pH, while elongation of fibril-seeds made from recombinant protein has only been achieved at low pH or at neutral pH in the presence of detergents or cosolvents. Here we describe a systematic study of the effect of 11 physiologically relevant factors on beta(2)m fibrillogenesis at pH 7.0 without denaturants. By comparing the results obtained for the wild-type protein with those of two variants (DeltaN6 and V37A), the role of protein stability in fibrillogenesis is explored. We show that DeltBiochemistryA systematic study of the effect of physiological factors on beta2-microglobulin amyloid formation at neutral pH.PMC7618240069064SF16972Radford SEHewitt EWTennent GAMorten IJMyers SLJones SJahn TRfalseA systematic study of the effect of physiological factors on beta2-microglobulin amyloid formation at neutral pH.Beta(2)-microglobulin (beta(2)m) forms amyloid fibrils that deposit in the musculo-skeletal system in patients undergoing long-term hemodialysis. How beta(2)m self-assembles in vivo is not understood, since the monomeric wild-type protein is incapable of forming fibrils in isolation in vitro at neutral pH, while elongation of fibril-seeds made from recombinant protein has only been achieved at low pH or at neutral pH in the presence of detergents or cosolvents. Here we describe a systematic study of the effect of 11 physiologically relevant factors on beta(2)m fibrillogenesis at pH 7.0 without denaturants. By comparing the results obtained for the wild-type protein with those of two variants (DeltaN6 and V37A), the role of protein stability in fibrillogenesis is explored. We show that Delt2006-01-01T00:00:00Z2006 Feb2026-06-04T09:46:21.256Z2026-05-07T03:12:53.846ZS-EPMC76182401647582010.1021/bi052434i