Insertion of heme b into the structure of the Cys34-carbamidomethylated human lipocalin α(1)-microglobulin: formation of a [(heme)(2) (α(1)-Microglobulin)](3) complex

Chembiochem. 2012 Apr 16;13(6):879-87. doi: 10.1002/cbic.201100808.

Abstract

α(1)-Microglobulin (α(1)m) is a 26 kDa plasma and tissue protein belonging to the lipocalin protein family. Previous investigations indicate that the protein interacts with heme and suggest that it has a function in heme metabolism. However, detailed characterizations of the α(1)m-heme interactions are lacking. Here, we report for the first time the preparation and analysis of a stable α(1)m-heme complex upon carbamidomethylation of the reactive Cys34 by using recombinantly expressed human α(1)m. Analytical size-exclusion chromatography coupled with a diode-array absorbance spectrophotometry demonstrates that at first an α(1)m-heme monomer is formed. Subsequently, a second heme triggers oligomerization that leads to trimerization. The resulting (α(1)m[heme](2))(3) complex was characterized by resonance Raman and EPR spectroscopy, which support the presence of two ferrihemes, thus indicating an unusual spin-state admixed ground state with S=(3)/(2), (5)/(2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alpha-Globulins / chemistry*
  • Alpha-Globulins / metabolism
  • Chromatography, Gel / methods
  • Heme / chemistry*
  • Heme / metabolism
  • Humans
  • Lipocalins / chemistry*
  • Lipocalins / metabolism
  • Protein Folding
  • Spectrophotometry

Substances

  • Alpha-Globulins
  • Lipocalins
  • alpha-1-microglobulin
  • Heme