alpha 1-Microglobulin destroys the proteinase inhibitory activity of alpha 1-inhibitor-3 by complex formation.
The immunoregulatory plasma protein alpha 1-microglobulin (alpha 1-m) and the proteinase inhibitor alpha 1-inhibitor-3 (alpha 1I3) form a complex in rat plasma. In the present work, it was demonstrated that the alpha 1I3.alpha 1-m complex has no inhibitory activity, the bait region was not cleaved by low amounts of proteinases, and it was unable to covalently incorporate proteinases. The results also indicated that the thiolester bond of the alpha 1I3.alpha 1-m complex was broken. The alpha 1I3.alpha 1-m complex was cleared from the circulation much faster than native alpha 1I3, with a half-life of approximately 7 min. Structurally, however, the alpha 1I3.alpha 1-m complex was similar to native alpha 1I3 rather than alpha 1I3 cleaved by proteinases. It is speculated that the role of alpha 1-m is to destroy the function of alpha 1I3 by blocking the bait region and breaking the thiolester and causing its physical elimination by rapid clearing from the blood circulation. It is also possible that the formation of complexes between alpha 1-m and alpha 1I3 may serve as a mean to regulate the function of alpha 1-m since its complex with alpha 1I3 is taken up rapidly by cellular receptors for alpha-macroglobulins.
Falkenberg
C
C
Department of Medical and Physiological Chemistry, University of Lund, Sweden.
Allhorn
M
M
Thøgersen
I B
IB
Valnickova
Z
Z
Pizzo
S V
SV
Salvesen
G
G
Akerström
B
B
Enghild
J J
JJ
D000209:Acute-Phase Proteins / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D000510:Alpha-Globulins / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D004952:Esters / Q000378:metabolism; D008744:Methylamines / Q000378:metabolism; D008968:Molecular Conformation; D011480:Protease Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000209:Acute-Phase Proteins; D000510:Alpha-Globulins; D004952:Esters; D008744:Methylamines; D011480:Protease Inhibitors; D013438:Sulfhydryl Compounds; C017894:alpha 1-inhibitor 3; C016001:alpha-1-microglobulin; C027451:methylamine