Analysis of human/mouse interleukin-6 hybrid proteins: Both amino and carboxy termini of human interleukin-6 are required for in vitro receptor binding

Maria Teresa Fiorillo, Andrea Cabibbo, Paola Iacopetti, Elena Fattori, Gennaro Ciliberto

Research output: Contribution to journalArticlepeer-review

Abstract

The multifunctional cytokine interleukin-6 (IL-6) is a single polypeptide chain consisting of 184 amino acids in man and 187 amino acids in mouse. Despite the relatively high degree of sequence similarity of these two molecules (about 57%), the biological activity in mouse and human IL-6 shows species specificity. Starting with this observation, we constructed interspecies hybrids with the goal of defining which segments of the human IL-6 molecule are involved in human receptor binding. In this manner we generated multiple amino acid substitution mutants which do not contain insertions or deletions as compared with the parental proteins, and which, therefore, should not show dramatic changes in folding. Using two biological assays on cells of human and mouse origin and a recently developed in vitro binding assay to recombinant soluble human IL-6 receptor, we obtained results which indicate that both the amino and carboxy termini are necessary and sufficient for efficient binding, but that the carboxy terminus plays the dominant role in receptor recognition.

Original languageEnglish
Pages (from-to)2609-2615
Number of pages7
JournalEuropean Journal of Immunology
Volume22
Issue number10
Publication statusPublished - Oct 1992

ASJC Scopus subject areas

  • Immunology

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