Solution structure and dynamics of myeloid progenitor inhibitory factor-1 (MPIF-1), a novel monomeric CC chemokine

J Biol Chem. 2001 Feb 16;276(7):4909-16. doi: 10.1074/jbc.M005085200. Epub 2000 Nov 1.


MPIF-1, a CC chemokine, is a specific inhibitor of myeloid progenitor cells and is the most potent activator of monocytes. The solution structure of myeloid progenitor inhibitor factor-1 (MPIF-1) has been determined by NMR spectroscopy. The structure reveals that MPIF-1 is a monomer with a well defined core except for termini residues and adopts the chemokine fold of three beta-strands and an overlying alpha-helix. In addition to the four cysteines that characterize most chemokines, MPIF-1 has two additional cysteines that form a disulfide bond. The backbone dynamics indicate that the disulfide bonds and the adjacent residues that include the functionally important N-terminal and N-terminal loop residues show significant dynamics. MPIF-1 is a highly basic protein (pI >9), and the structure reveals distinct positively charged pockets that could be correlated to proteoglycan binding. MPIF-1 is processed from a longer proprotein at the N terminus and the latter is also functional though with reduced potency, and both proteins exist as monomers under a variety of solution conditions. MPIF-1 is therefore unique because longer proproteins of all other chemokines oligomerize in solution. The MPIF-1 structure should serve as a template for future functional studies that could lead to therapeutics for preventing chemotherapy-associated myelotoxicity.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chemokines, CC / chemistry*
  • Chemokines, CC / genetics
  • Chemokines, CC / metabolism
  • Escherichia coli / genetics
  • Heparin / metabolism
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Sequence Homology, Amino Acid
  • Transformation, Bacterial
  • Ultracentrifugation


  • CCL23 protein, human
  • Chemokines, CC
  • Heparin

Associated data

  • PDB/1G91