alpha2-Macroglobulin, the main serum antiprotease, binds beta2-microglobulin, the light chain of the class I major histocompatibility complex, which is involved in human disease.
beta(2)-Microglobulin, a 12 kDa protein forming part of the class I HLA (histocompatibility locus antigen) major histocompatibility complex, has been used as a prognosis factor for multiple myeloma and as a marker of renal function, and has been shown to be involved in the pathogenesis of dialysis-related amyloidosis. alpha(2)-Macroglobulin has the ability to bind a wide range of physiologically important molecules, thereby influencing their metabolic impact. In this study we show by Western blotting analysis that beta(2)-microglobulin binds to alpha(2)-macroglobulin in vitro. This binding was confirmed by BIAcore analysis, and was shown by ELISA to be concentration-dependent. The sequences of the binding peptides in the mature beta(2)-microglobulin molecule were identified by Spot multiple peptide synthesis and alpha(2)-macroglobulin binding studies. In conclusion, beta(2)-microglobulin interacts specifically with the universal antiprotease a(2)-macroglobulin. The identification of this interaction brings into question some of the axioms on the metabolism of beta(2)-microglobulin, and may help to explain the clinical findings observed in b(2)-microglobulin-related diseases.
Gouin-Charnet
A
A
Institut de Génétique Humaine (I.G.H.), CNRS UPR 1142, 141, rue de la Cardonille, 34090 Montpellier Cedex 5, France. angel.argiles@igh.cnrs.fr
Laune
D
D
Granier
C
C
Mani
J C
JC
Pau
B
B
Mourad
G
G
Argilés
A
A
D000686:Amyloidosis / Q000378:metabolism; D001665:Binding Sites; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D000511:alpha-Macroglobulins / Q000737:chemistry*; D001613:beta 2-Microglobulin / Q000737:chemistry*
D000511:alpha-Macroglobulins; D001613:beta 2-Microglobulin