Structure-based mutational analyses in FGF7 identify new residues involved in specific interaction with FGFR2IIIb

Ifat Sher, Brian K. Yeh, Moosa Mohammadi, Noam Adir, Dina Ron*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Receptor binding specificity is an essential element in regulating the diverse activities of fibroblast growth factors (FGFs). FGF7 is ideal to study how this specificity is conferred at the structural level, as it interacts exclusively with one isoform of the FGF-receptor (FGFR) family, known as FGFR2IIIb. Previous mutational analysis suggested the importance of the β4/β5 loop of FGF7 in specific receptor recognition. Here a theoretical model of FGFR2IIIb/FGF7 complex showed that this loop interacts with the FGFR2IIIb unique exon. In addition, the model revealed new residues that either directly interact with the FGFR2IIIb unique exon (Asp63, Leu142) or facilitate this interaction (Arg65). Mutations in these residues reduced both receptor binding affinity and biological activity of FGF7. Altogether, these results provide the basis for understanding how receptor-binding specificity of FGF7 is conferred at the structural level.

Original languageEnglish
Pages (from-to)150-154
Number of pages5
JournalFEBS Letters
Volume552
Issue number2-3
DOIs
StatePublished - 25 Sep 2003
Externally publishedYes

Funding

FundersFunder number
Gesellschaft für Biotechnologische Forschüng
Israel and German Ministry of Science

    Keywords

    • FGF10
    • FGF7
    • FGF7/FGFR complex
    • Fibroblast growth factor
    • Fibroblast growth factor receptor
    • Mutagenesis

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