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alpha 1-Microglobulin destroys the proteinase inhibitory activity of alpha 1-inhibitor-3 by complex formation.

Publication ,  Journal Article
Falkenberg, C; Allhorn, M; Thøgersen, IB; Valnickova, Z; Pizzo, SV; Salvesen, G; Akerström, B; Enghild, JJ
Published in: J Biol Chem
March 3, 1995

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.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 3, 1995

Volume

270

Issue

9

Start / End Page

4478 / 4483

Location

United States

Related Subject Headings

  • Sulfhydryl Compounds
  • Rats, Sprague-Dawley
  • Rats
  • Protease Inhibitors
  • Molecular Conformation
  • Methylamines
  • Esters
  • Biochemistry & Molecular Biology
  • Animals
  • Alpha-Globulins
 

Citation

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Falkenberg, C., Allhorn, M., Thøgersen, I. B., Valnickova, Z., Pizzo, S. V., Salvesen, G., … Enghild, J. J. (1995). alpha 1-Microglobulin destroys the proteinase inhibitory activity of alpha 1-inhibitor-3 by complex formation. J Biol Chem, 270(9), 4478–4483. https://doi.org/10.1074/jbc.270.9.4478
Falkenberg, C., M. Allhorn, I. B. Thøgersen, Z. Valnickova, S. V. Pizzo, G. Salvesen, B. Akerström, and J. J. Enghild. “alpha 1-Microglobulin destroys the proteinase inhibitory activity of alpha 1-inhibitor-3 by complex formation.J Biol Chem 270, no. 9 (March 3, 1995): 4478–83. https://doi.org/10.1074/jbc.270.9.4478.
Falkenberg C, Allhorn M, Thøgersen IB, Valnickova Z, Pizzo SV, Salvesen G, et al. alpha 1-Microglobulin destroys the proteinase inhibitory activity of alpha 1-inhibitor-3 by complex formation. J Biol Chem. 1995 Mar 3;270(9):4478–83.
Falkenberg, C., et al. “alpha 1-Microglobulin destroys the proteinase inhibitory activity of alpha 1-inhibitor-3 by complex formation.J Biol Chem, vol. 270, no. 9, Mar. 1995, pp. 4478–83. Pubmed, doi:10.1074/jbc.270.9.4478.
Falkenberg C, Allhorn M, Thøgersen IB, Valnickova Z, Pizzo SV, Salvesen G, Akerström B, Enghild JJ. alpha 1-Microglobulin destroys the proteinase inhibitory activity of alpha 1-inhibitor-3 by complex formation. J Biol Chem. 1995 Mar 3;270(9):4478–4483.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 3, 1995

Volume

270

Issue

9

Start / End Page

4478 / 4483

Location

United States

Related Subject Headings

  • Sulfhydryl Compounds
  • Rats, Sprague-Dawley
  • Rats
  • Protease Inhibitors
  • Molecular Conformation
  • Methylamines
  • Esters
  • Biochemistry & Molecular Biology
  • Animals
  • Alpha-Globulins