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

FEBS Letters

Mohammadi, Moosa³  Sher, Ifat¹  Yeh, Brian K³  Ron, Dina¹  Adir, Noam² 

[1] Department of Biology, Technion – Israel Institute of Technology, Haifa 32000, Israel;Department of Chemistry, Technion – Israel Institute of Technology, Haifa 32000, Israel;Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA

关键词: Fibroblast growth factor;    FGF7;    FGF10;    Fibroblast growth factor receptor;    Mutagenesis;    FGF7/FGFR complex;    FGF;    fibroblast growth factor;    FGFR;    fibroblast growth factor receptor;    KGF;    keratinocyte growth factor;    KGFR;    keratinocyte growth factor receptor;    SDS–PAGE;    sodium dodecyl sulfate–polyacrylamide gel electrophoresis;   

DOI  :  10.1016/S0014-5793(03)00909-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown