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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/106399
- author
- Allhorn, Maria
LU
; Berggård, Tord
LU
; Nordberg, Jonas
LU
; Olsson, Martin L
LU
and Åkerström, Bo
LU
- organization
- publishing date
- 2002
- 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
- 2016-04-01 11:37:21
- date last changed
- 2019-08-14 02:19:09
@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}},
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}},
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.}},
url = {{http://bloodjournal.hematologylibrary.org/cgi/content/full/99/6/1894}},
volume = {{99}},
year = {{2002}},
}