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

R. C. Robinson, L. M. Grey, D. Staunton, H. Vankelecom, A. B. Vernallis, J. F. Moreau, D. I. Stuart, J. K. Heath, E. Y. Jones

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

The structure of murine leukemia inhibitory factor (LIF) has been determined by X-ray crystallography at 2.0 Å resolution. The main chain fold conforms to the four α-helix bundle topology previously observed for several members of the hematopoletic 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.

Original languageEnglish
Pages (from-to)1101-1116
Number of pages16
JournalCell
Volume77
Issue number7
DOIs
Publication statusPublished - Jul 1 1994
Externally publishedYes

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Leukemia Inhibitory Factor Receptor alpha Subunit
OSM-LIF Receptors
Recombinant Fusion Proteins
Leukemia Inhibitory Factor
Growth Inhibitors
Cytokine Receptors
Lymphokines
X ray crystallography
Interleukin-6
Animals
Crystal structure
Ligands
Growth Hormone
Oncostatin M
Ciliary Neurotrophic Factor
Granulocyte Colony-Stimulating Factor
Topology
Cytokines
Molecules

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Robinson, R. C., Grey, L. M., Staunton, D., Vankelecom, H., Vernallis, A. B., Moreau, J. F., ... Jones, E. Y. (1994). The crystal structure and biological function of leukemia inhibitory factor: Implications for receptor binding. Cell, 77(7), 1101-1116. https://doi.org/10.1016/0092-8674(94)90449-9

The crystal structure and biological function of leukemia inhibitory factor : Implications for receptor binding. / Robinson, R. C.; Grey, L. M.; Staunton, D.; Vankelecom, H.; Vernallis, A. B.; Moreau, J. F.; Stuart, D. I.; Heath, J. K.; Jones, E. Y.

In: Cell, Vol. 77, No. 7, 01.07.1994, p. 1101-1116.

Research output: Contribution to journalArticle

Robinson, RC, Grey, LM, Staunton, D, Vankelecom, H, Vernallis, AB, Moreau, JF, Stuart, DI, Heath, JK & Jones, EY 1994, 'The crystal structure and biological function of leukemia inhibitory factor: Implications for receptor binding', Cell, vol. 77, no. 7, pp. 1101-1116. https://doi.org/10.1016/0092-8674(94)90449-9
Robinson, R. C. ; Grey, L. M. ; Staunton, D. ; Vankelecom, H. ; Vernallis, A. B. ; Moreau, J. F. ; Stuart, D. I. ; Heath, J. K. ; Jones, E. Y. / The crystal structure and biological function of leukemia inhibitory factor : Implications for receptor binding. In: Cell. 1994 ; Vol. 77, No. 7. pp. 1101-1116.
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