title: alpha2-Macroglobulin and haptoglobin suppress amyloid formation by interacting with prefibrillar protein species.
abstract: alpha(2)-Macroglobulin (alpha(2)M) and haptoglobin (Hp) are both abundant secreted glycoproteins that are best known for their protease trapping and hemoglobin binding activities, respectively. Like the small heat shock proteins, both these glycoproteins have in common the ability to protect a range of proteins from stress-induced amorphous aggregation and have been described as extracellular chaperones. Using an array of biophysical techniques, this study establishes that in vitro at substoichiometric levels and under physiological conditions alpha(2)M and Hp both inhibit the formation of amyloid fibrils from a range of proteins. We also provide evidence that both alpha(2)M and Hp interact with prefibrillar species to maintain the solubility of amyloidogenic proteins. These findings suggest that both alpha(2)M and Hp are likely to play an important role in controlling the inappropriate aggregation of proteins in the extracellular environment.
authors.affiliation: School of Biological Sciences, University of Wollongong, Northfields Avenue, Wollongong, New South Wales 2522, Australia.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Yerbury
authors.forename: Janet R
authors.initials: JR
authors.lastname: Kumita
authors.forename: Sarah
authors.initials: S
authors.lastname: Meehan
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
authors.forename: Mark R
authors.initials: MR
authors.lastname: Wilson
mesh_terms: D000682:Amyloid / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D006242:Haptoglobins / Q000737:chemistry* / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D000511:alpha-Macroglobulins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D006242:Haptoglobins; D006454:Hemoglobins; D010446:Peptide Fragments; D000511:alpha-Macroglobulins; C075222:amyloid beta-protein (1-42)