Processing of the lipocalin alpha(1)-microglobulin by hemoglobin induces heme-binding and heme-degradation properties.
Författare
Summary, in English
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)
Avdelning/ar
Publiceringsår
2002
Språk
Engelska
Sidor
1894-1901
Publikation/Tidskrift/Serie
Blood
Volym
99
Issue
6
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
American Society of Hematology
Ämne
- Hematology
Nyckelord
- 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
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1528-0020