@article{0405a1beac2b4535b1e9869085e99559,
title = "The crystal structure and biological function of leukemia inhibitory factor: Implications for receptor binding",
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.",
author = "Robinson, {R. C.} and Grey, {L. M.} and D. Staunton and H. Vankelecom and Vernallis, {A. B.} and Moreau, {J. F.} and Stuart, {D. I.} and Heath, {J. K.} and Jones, {E. Y.}",
note = "Funding Information: L. M. G. should be considered the primary author for the protein biochemical work. We thank J. Pitt and S. Cole for assistance with protein production; D. Harvey for mass spectroscopy; T. Willis for protein sequencing and amino acid analysis; C. Piquet-Pellorce for development of bioassays; K. Harlos and the staff at the SRS Daresbury Labratory in Warrington, England and at the Photon Factory in Japan for help with X-ray data collection; and R. Bryan and R. Esnouf for computing facilities. We are grateful to S. Lee for help with the preparation of figures. The Growth Factor Group is supported by the Cancer Research Campaign (CRC). The Oxford Centre for Molecular Sciences is supported by the SERC and the Medical Research Council (MRC). E. Y. J. is supported by a Royal Society Research Fellowship, and R. C. R. is supported by an MRC research studentship. J.-F. M. is supported by the Centre National de la Recherche Scientifique. L. M. G. is supported by a CRC studentship: A. V. is supported by an American Cancer Society Fellowship; and H. V. is supported by fellowships from the European Molecular Biology Organization, the European Science Foundation, and the Royal Society. Atomic coordinates for murine LIF have been deposited with the Protein Data Bank, Brookhaven National Laboratory. Prerelease co-ordinates are available from E. Y. J.; e-mail address is WON@LMB. BIOP.OX.AC.UK. Correspondence should be addressed to J. K. Heath.",
year = "1994",
month = jul,
day = "1",
doi = "10.1016/0092-8674(94)90449-9",
language = "English",
volume = "77",
pages = "1101--1116",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "7",
}