Localization of functional receptor epitopes on the structure of ciliary neurotrophic factor indicates a conserved, function-related epitope topography among helical cytokines.

The Journal of Biological Chemistry
N PanayotatosN Q McDonald

Abstract

By rational mutagenesis, receptor-specific functional analysis, and visualization of complex formation in solution, we identified individual amino acid side chains involved specifically in the interaction of ciliary neurotrophic factor (CNTF) with CNTFR alpha and not with the beta-components, gp130 and LIFR. In the crystal structure, the side chains of these residues, which are located in helix A, the AB loop, helix B, and helix D, are surface accessible and are clustered in space, thus constituting an epitope for CNTFR alpha. By the same analysis, a partial epitope for gp130 was also identified on the surface of helix A that faces away from the alpha-epitope. Superposition of the CNTF and growth hormone structures showed that the location of these epitopes on CNTF is analogous to the location of the first and second receptor epitopes on the surface of growth hormone. Further comparison with proposed binding sites for alpha- and beta-receptors on interleukin-6 and leukemia inhibitory factor indicated that this epitope topology is conserved among helical cytokines. In each case, epitope I is utilized by the specificity-conferring component, whereas epitopes II and III are used by accessory components. Thus, in addition to a comm...Continue Reading

References

Jul 5, 1991·Science·S DavisG D Yancopoulos
Sep 1, 1991·Journal of Neurochemistry·P MasiakowskiN Panayotatos
Dec 5, 1993·Journal of Molecular Biology·B C Cunningham, J A Wells
May 1, 1994·Trends in Neurosciences·R M LindsayP S DiStefano
Feb 1, 1993·Current Opinion in Neurobiology·S Davis, G D Yancopoulos

❮ Previous
Next ❯

Citations

Mar 21, 2000·Journal of Neuroscience Research·M ThierS Rose-John
May 1, 1997·Protein Science : a Publication of the Protein Society·R J SimpsonL D Ward
May 17, 2000·Pharmaceutica acta Helvetiae·M W SleemanS J Wiegand
Oct 24, 1998·Trends in Neurosciences·C F Ibáñez
Oct 3, 1999·European Journal of Biochemistry·I TackenG Müller-Newen
Oct 27, 2010·Proceedings of the National Academy of Sciences of the United States of America·Francois RousseauHugues Gascan
Mar 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kang ZhangGeorge A Williams
Aug 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·A Di MarcoR Laufer
Jul 17, 2003·Endocrinology·Nicholas Underhill-DayJohn K Heath
Jun 1, 1996·Molecular Neurobiology·M InoueH Noguchi
Jul 5, 2005·Expert Opinion on Investigational Drugs·K J KallenS Rose-John
Mar 1, 1997·Expert Opinion on Investigational Drugs·K J KallenS Rose-John
Jan 29, 2016·Cytokine·Sarah PasquinJean-François Gauchat
Dec 21, 2011·Progress in Retinal and Eye Research·Rong WenPaul A Sieving
Feb 12, 2004·Pediatric Transplantation·Philip D Acott, Jeffrey M Pernica
Dec 2, 2004·Brain Research. Brain Research Reviews·Cecilia Vergara, Beatriz Ramirez
Dec 14, 2004·Cytokine·Olga P YatsenkoSergey V Sennikov
Jul 26, 2016·Frontiers in Neuroscience·Martina SenzacquaAntonio Giordano
May 2, 1997·Journal of Molecular Biology·G Y XuD A Cumming
Oct 27, 2017·Artificial Cells, Nanomedicine, and Biotechnology·Maryam GhasemiNosratollah Zarghami
Aug 19, 2000·The Journal of Biological Chemistry·V A BartonJ K Heath
Jun 17, 2000·Endocrine Reviews·C J Auernhammer, S Melmed
Jun 5, 1998·The Journal of Biological Chemistry·M G HindsR S Norton
Dec 20, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S PflanzG Müller-Newen

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.