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

Maria Allhorn, Tord Berggård, Jonas Nordberg, Martin L Olsson, Bo Åkerström

Research output: Contribution to journalArticlepeer-review

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)
Original languageEnglish
Pages (from-to)1894-1901
JournalBlood
Volume99
Issue number6
Publication statusPublished - 2002

Subject classification (UKÄ)

  • Hematology

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

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