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

doi:10.1016/0092-8674(94)90449-9

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

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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 language	English
Pages (from-to)	1101-1116
Number of pages	16
Journal	Cell
Volume	77
Issue number	7
DOIs	https://doi.org/10.1016/0092-8674(94)90449-9
Publication status	Published - Jul 1 1994
Externally published	Yes

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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., Stuart, D. I., Heath, J. K., & 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

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abstract = "The structure of murine leukemia inhibitory factor (LIF) has been determined by X-ray crystallography at 2.0 {\AA} 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.",

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AU - Robinson, R. C.

AU - Grey, L. M.

AU - Staunton, D.

AU - Vankelecom, H.

AU - Vernallis, A. B.

AU - Moreau, J. F.

AU - Stuart, D. I.

AU - Heath, J. K.

AU - Jones, E. Y.

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N2 - 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.

AB - 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.

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10.1016/0092-8674(94)90449-9