Acute phase proteins are major clients for the chaperone action of α₂-macroglobulin in human plasma.
Extracellular protein misfolding is implicated in many age-related diseases including Alzheimer's disease, macular degeneration and arthritis. In this study, putative endogenous clients for the chaperone activity of α₂-macroglobulin (α₂M) were identified after human plasma was subjected to physiologically relevant sheer stress at 37 °C for 10 days. Western blot analysis showed that four major acute phase proteins: ceruloplasmin, fibrinogen, α₁-acid glycoprotein and complement component 3, preferentially co-purified with α₂M after plasma was stressed. Furthermore, the formation of complexes between α₂M and these putative chaperone clients, detected by sandwich ELISA, was shown to be enhanced in response to stress. These results support the hypothesis that α₂M plays an important role in extracellular proteostasis by sequestering misfolded proteins and targeting them for disposal, particularly during acute phase reactions.
Department of Chemistry, University of Cambridge, Cambridge, UK.
Amy R
AR
Wyatt
Nathan W
NW
Zammit
Mark R
MR
Wilson
D000209:Acute-Phase Proteins / Q000378:metabolism*; D015153:Blotting, Western; D002570:Ceruloplasmin / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D009961:Orosomucoid / Q000378:metabolism; D011485:Protein Binding; D033081:Shear Strength; D013696:Temperature; D000511:alpha-Macroglobulins / Q000378:metabolism*
D000209:Acute-Phase Proteins; D003176:Complement C3; D009961:Orosomucoid; D000511:alpha-Macroglobulins; D005340:Fibrinogen; D002570:Ceruloplasmin