[1H,13C] NMR determination of the order of lobe loading of human transferrin with iron: comparison with other metal ions

FEBS Lett. 1998 Feb 6;422(3):315-20. doi: 10.1016/s0014-5793(98)00034-9.


Human serum transferrin (hTF) is a single-chain bilobal glycoprotein (80 kDa) which transports Fe3+ and a variety of other metal ions in blood. Only diferric transferrin, not the apo-protein, binds strongly to transferrin receptors and is taken up by cells via receptor-mediated endocytosis. We show here that 2D [1H,13C] NMR studies of recombinant epsilon-[13C]Met-hTF allow the order of lobe loading with various metal ions, including Fe3+, to be determined. In particular, the resonance for Met-464, a residue in the hydrophobic patch of helix 5, is very sensitive to iron binding in the C-lobe. The selectivity of lobe loading with Fe3+ is compared to loading with Fe2+ (which binds as Fe3+), Al3+, Ga3+ and Bi3+. Similar changes in shifts of the Met residues are observed for these metal ions, suggesting that they induce similar conformational changes in the protein.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aluminum / chemistry
  • Animals
  • Bismuth / chemistry
  • Cells, Cultured
  • Cricetinae
  • Ferric Compounds / chemistry
  • Gallium / chemistry
  • Humans
  • Iron / chemistry*
  • Magnetic Resonance Spectroscopy
  • Metals / chemistry*
  • Protein Binding
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Transferrin / chemistry*
  • Transferrin / genetics


  • Ferric Compounds
  • Metals
  • Recombinant Proteins
  • Transferrin
  • Gallium
  • Aluminum
  • Iron
  • Bismuth