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

Falkenberg, Cecilia LU ; Allhorn, Maria LU ; Thogersen, Ida B; Valnickova, Zuzana; Pizzo, Salvatore V; Salvesen, Guy; Åkerström, Bo LU and Enghild, Jan J (1995) In Journal of Biological Chemistry 270(9). p.4478-4483
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
270
issue
9
pages
4478 - 4483
publisher
ASBMB
external identifiers
  • pmid:7533162
ISSN
1083-351X
language
English
LU publication?
yes
id
06e614e3-b329-4b1c-9665-d25a73f29f71 (old id 1109684)
alternative location
http://www.jbc.org/cgi/reprint/270/9/4478
date added to LUP
2008-07-29 13:24:21
date last changed
2016-04-15 20:41:52
@article{06e614e3-b329-4b1c-9665-d25a73f29f71,
  abstract     = {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.},
  author       = {Falkenberg, Cecilia and Allhorn, Maria and Thogersen, Ida B and Valnickova, Zuzana and Pizzo, Salvatore V and Salvesen, Guy and Åkerström, Bo and Enghild, Jan J},
  issn         = {1083-351X},
  language     = {eng},
  number       = {9},
  pages        = {4478--4483},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {alpha 1-Microglobulin destroys the proteinase inhibitory activity of alpha 1-inhibitor-3 by complex formation},
  volume       = {270},
  year         = {1995},
}