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 | |
| 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
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 journal › Article
}
TY - JOUR
T1 - The crystal structure and biological function of leukemia inhibitory factor
T2 - Implications for receptor binding
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.
PY - 1994/7/1
Y1 - 1994/7/1
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.
UR - http://www.scopus.com/inward/record.url?scp=0028363673&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028363673&partnerID=8YFLogxK
U2 - 10.1016/0092-8674(94)90449-9
DO - 10.1016/0092-8674(94)90449-9
M3 - Article
C2 - 8020098
AN - SCOPUS:0028363673
VL - 77
SP - 1101
EP - 1116
JO - Cell
JF - Cell
SN - 0092-8674
IS - 7
ER -