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Detailed analysis of the IL-5-IL-5R alpha interaction: characterization of crucial residues on the ligand and the receptor.

1995; Springer Nature; Volume: 14; Issue: 14 Linguagem: Inglês

10.1002/j.1460-2075.1995.tb07345.x

1460-2075

Sigrid Cornelis, Geert Plaetinck, René Devos, José Van der Heyden, Jan Tavernier, Colin J. Sanderson, Yves Guisez, Walter Fiers,

Eosinophilic Esophagitis

Research Article17 July 1995free access Detailed analysis of the IL-5-IL-5R alpha interaction: characterization of crucial residues on the ligand and the receptor. S. Cornelis S. Cornelis Roche Research Gent, Belgium. Search for more papers by this author G. Plaetinck G. Plaetinck Roche Research Gent, Belgium. Search for more papers by this author R. Devos R. Devos Roche Research Gent, Belgium. Search for more papers by this author J. Van der Heyden J. Van der Heyden Roche Research Gent, Belgium. Search for more papers by this author J. Tavernier J. Tavernier Roche Research Gent, Belgium. Search for more papers by this author C.J. Sanderson C.J. Sanderson Roche Research Gent, Belgium. Search for more papers by this author Y. Guisez Y. Guisez Roche Research Gent, Belgium. Search for more papers by this author W. Fiers W. Fiers Roche Research Gent, Belgium. Search for more papers by this author S. Cornelis S. Cornelis Roche Research Gent, Belgium. Search for more papers by this author G. Plaetinck G. Plaetinck Roche Research Gent, Belgium. Search for more papers by this author R. Devos R. Devos Roche Research Gent, Belgium. Search for more papers by this author J. Van der Heyden J. Van der Heyden Roche Research Gent, Belgium. Search for more papers by this author J. Tavernier J. Tavernier Roche Research Gent, Belgium. Search for more papers by this author C.J. Sanderson C.J. Sanderson Roche Research Gent, Belgium. Search for more papers by this author Y. Guisez Y. Guisez Roche Research Gent, Belgium. Search for more papers by this author W. Fiers W. Fiers Roche Research Gent, Belgium. Search for more papers by this author Author Information S. Cornelis1, G. Plaetinck1, R. Devos1, J. Van der Heyden1, J. Tavernier1, C.J. Sanderson1, Y. Guisez1 and W. Fiers1 1Roche Research Gent, Belgium. The EMBO Journal (1995)14:3395-3402https://doi.org/10.1002/j.1460-2075.1995.tb07345.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info The receptor for interleukin-5 (IL-5) is composed of two different subunits. The IL-5 receptor alpha (IL-5R alpha) is required for ligand-specific binding while association with the beta-chain results in increased binding affinity. Murine IL-5 (mIL-5) has similar activity on human and murine cells, whereas human IL-5 (hIL-5) has marginal activity on murine cells. We found that the combined substitution of K84 and N108 on hIL-5 by their respective murine counterpart yields a molecule which is as potent as mIL-5 for growth stimulation of a murine cell line. Since the unidirectional species specificity is due only to the interaction with the IL-5R alpha subunit, we have used chimeric IL-5R alpha molecules to define regions of hIL-5R alpha involved in species-specific hIL-5 ligand binding. We found that this property is largely determined by the NH2-terminal module of hIL-5R alpha, and detailed analysis defined D56 and to a lesser extent E58 as important for binding. Moreover, two additional residues, D55 and Y57, were identified by alanine scanning mutagenesis within the same region. Based on the observed homology between the NH2-terminal module and the membrane proximal (WSXWS-containing) module of hIL-5R alpha we located this stretch of four amino acid residues (D55, D56, Y57 and E58) in the loop region that connects the C and D beta-strands on the proposed tertiary structure of the NH2-terminal module.(ABSTRACT TRUNCATED AT 250 WORDS) Previous ArticleNext Article Volume 14Issue 141 July 1995In this issue RelatedDetailsLoading ...