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Processing of the lipocalin alpha(1)-microglobulin by hemoglobin induces heme-binding and heme-degradation properties.

Allhorn, Maria LU ; Berggård, Tord LU ; Nordberg, Jonas LU ; Olsson, Martin L LU and Åkerström, Bo LU (2002) In Blood 99(6). p.1894-1901
Abstract
alpha(1)-Microglobulin is a 26-kd protein, widespread in plasma and tissues and well-conserved among vertebrates. alpha(1)-Microglobulin belongs to the lipocalins, a protein superfamily with highly conserved 3-dimensional structures, forming an internal ligand binding pocket. The protein, isolated from urine, has a heterogeneous yellow-brown chromophore bound covalently to amino acid side groups around the entrance of the lipocalin pocket. alpha(1)-Microglobulin is found in blood both in free form and complex-bound to immunoglobulin A (IgA) via a half-cystine residue at position 34. It is shown here that an alpha(1)-microglobulin species, which we name t-alpha(1)-microglobulin (t = truncated), with a free Cys34 thiol group, lacking its... (More)
alpha(1)-Microglobulin is a 26-kd protein, widespread in plasma and tissues and well-conserved among vertebrates. alpha(1)-Microglobulin belongs to the lipocalins, a protein superfamily with highly conserved 3-dimensional structures, forming an internal ligand binding pocket. The protein, isolated from urine, has a heterogeneous yellow-brown chromophore bound covalently to amino acid side groups around the entrance of the lipocalin pocket. alpha(1)-Microglobulin is found in blood both in free form and complex-bound to immunoglobulin A (IgA) via a half-cystine residue at position 34. It is shown here that an alpha(1)-microglobulin species, which we name t-alpha(1)-microglobulin (t = truncated), with a free Cys34 thiol group, lacking its C-terminal tetrapeptide, LIPR, and with a more polar environment around the entrance of the lipocalin pocket, is released from IgA-alpha(1)-microglobulin as well as from free alpha(1)-microglobulin when exposed to the cytosolic side of erythrocyte membranes or to purified oxyhemoglobin. The processed t-alpha(1)-microglobulin binds heme and the alpha(1)-microglobulin-heme complex shows a time-dependent spectral rearrangement, suggestive of degradation of heme concomitantly with formation of a heterogeneous chromophore associated with the protein. The processed t-alpha(1)-microglobulin is found in normal and pathologic human urine, indicating that the cleavage process occurs in vivo. The results suggest that alpha(1)-microglobulin is involved in extracellular heme catabolism. (Blood. 2002;99:1894-1901) (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Pepsin A/metabolism, Kinetics, Protein Binding, *Protein Processing, Post-Translational, Radioactive Tracers, Support, Non-U.S. Gov't, Immunoglobulin A/metabolism, Hemoglobins/*metabolism/physiology, Human, Heme/*metabolism, Erythrocyte Membrane/metabolism, Disulfides/metabolism, Alpha-Globulins/chemistry/*metabolism/physiology
in
Blood
volume
99
issue
6
pages
1894 - 1901
publisher
American Society of Hematology
external identifiers
  • wos:000174355800004
  • pmid:11877257
ISSN
1528-0020
language
English
LU publication?
yes
id
ea2f6c9f-7e09-44fa-9195-d0567c9669cd (old id 106399)
alternative location
http://bloodjournal.hematologylibrary.org/cgi/content/full/99/6/1894
date added to LUP
2007-07-04 14:57:32
date last changed
2016-04-15 18:41:30
@article{ea2f6c9f-7e09-44fa-9195-d0567c9669cd,
  abstract     = {alpha(1)-Microglobulin is a 26-kd protein, widespread in plasma and tissues and well-conserved among vertebrates. alpha(1)-Microglobulin belongs to the lipocalins, a protein superfamily with highly conserved 3-dimensional structures, forming an internal ligand binding pocket. The protein, isolated from urine, has a heterogeneous yellow-brown chromophore bound covalently to amino acid side groups around the entrance of the lipocalin pocket. alpha(1)-Microglobulin is found in blood both in free form and complex-bound to immunoglobulin A (IgA) via a half-cystine residue at position 34. It is shown here that an alpha(1)-microglobulin species, which we name t-alpha(1)-microglobulin (t = truncated), with a free Cys34 thiol group, lacking its C-terminal tetrapeptide, LIPR, and with a more polar environment around the entrance of the lipocalin pocket, is released from IgA-alpha(1)-microglobulin as well as from free alpha(1)-microglobulin when exposed to the cytosolic side of erythrocyte membranes or to purified oxyhemoglobin. The processed t-alpha(1)-microglobulin binds heme and the alpha(1)-microglobulin-heme complex shows a time-dependent spectral rearrangement, suggestive of degradation of heme concomitantly with formation of a heterogeneous chromophore associated with the protein. The processed t-alpha(1)-microglobulin is found in normal and pathologic human urine, indicating that the cleavage process occurs in vivo. The results suggest that alpha(1)-microglobulin is involved in extracellular heme catabolism. (Blood. 2002;99:1894-1901)},
  author       = {Allhorn, Maria and Berggård, Tord and Nordberg, Jonas and Olsson, Martin L and Åkerström, Bo},
  issn         = {1528-0020},
  keyword      = {Pepsin A/metabolism,Kinetics,Protein Binding,*Protein Processing,Post-Translational,Radioactive Tracers,Support,Non-U.S. Gov't,Immunoglobulin A/metabolism,Hemoglobins/*metabolism/physiology,Human,Heme/*metabolism,Erythrocyte Membrane/metabolism,Disulfides/metabolism,Alpha-Globulins/chemistry/*metabolism/physiology},
  language     = {eng},
  number       = {6},
  pages        = {1894--1901},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Processing of the lipocalin alpha(1)-microglobulin by hemoglobin induces heme-binding and heme-degradation properties.},
  volume       = {99},
  year         = {2002},
}