Processing of the lipocalin alpha(1)-microglobulin by hemoglobin induces heme-binding and heme-degradation properties.
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.
Allhorn
Maria
M
Department of Cell and Molecular Biology, University Hospital, Lund University, S-221 84 Lund, Sweden.
Berggård
Tord
T
Nordberg
Jonas
J
Olsson
Martin L
ML
Akerström
Bo
B
D000510:Alpha-Globulins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D004220:Disulfides / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism; D006418:Heme / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007700:Kinetics; D010434:Pepsin A / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011849:Radioactive Tracers
D000510:Alpha-Globulins; D004220:Disulfides; D006454:Hemoglobins; D007070:Immunoglobulin A; D011849:Radioactive Tracers; C016001:alpha-1-microglobulin; D006418:Heme; D010434:Pepsin A