The crystal structure and biological function of leukemia inhibitory factor: implications for receptor binding

Cell. 1994 Jul 1;77(7):1101-16. doi: 10.1016/0092-8674(94)90449-9.


The structure of murine leukemia inhibitory factor (LIF) has been determined by X-ray crystallography at 2.0 A resolution. The main chain fold conforms to the four alpha-helix bundle topology previously observed for several members of the hematopoietic cytokine family. Of these, LIF shows closest structural homology to granulocyte colony-stimulating factor and growth hormone (GH). Sequence alignments for the functionally related molecules oncostatin M and ciliary neurotrophic factor, when mapped to the LIF structure, indicate regions of conserved surface character. Analysis of the biological function and receptor specificity of a series of human-mouse LIF chimeras implicate two regions of receptor interaction that are located in the fourth helix and the preceding loop. A model for receptor binding based on the structure of the GH ligand-receptor complex requires additional, novel features to account for these data.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • Growth Inhibitors / metabolism*
  • Interleukin-6*
  • Leukemia Inhibitory Factor
  • Leukemia Inhibitory Factor Receptor alpha Subunit
  • Ligands
  • Lymphokines / metabolism*
  • Lymphokines / ultrastructure*
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Receptors, Cytokine / metabolism
  • Receptors, OSM-LIF
  • Recombinant Fusion Proteins / chemistry
  • Sequence Alignment
  • Sequence Homology, Amino Acid


  • Growth Inhibitors
  • Interleukin-6
  • LIF protein, human
  • LIFR protein, human
  • Leukemia Inhibitory Factor
  • Leukemia Inhibitory Factor Receptor alpha Subunit
  • Lif protein, mouse
  • Lifr protein, mouse
  • Ligands
  • Lymphokines
  • Receptors, Cytokine
  • Receptors, OSM-LIF
  • Recombinant Fusion Proteins