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PMID:10830168

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Citation

Plotnikov, AN, Hubbard, SR, Schlessinger, J and Mohammadi, M (2000) Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity. Cell 101:413-24

Abstract

To elucidate the structural determinants governing specificity in fibroblast growth factor (FGF) signaling, we have determined the crystal structures of FGF1 and FGF2 complexed with the ligand binding domains (immunoglobulin-like domains 2 [D2] and 3 [D3]) of FGF receptor 1 (FGFR1) and FGFR2, respectively. Highly conserved FGF-D2 and FGF-linker (between D2-D3) interfaces define a general binding site for all FGF-FGFR complexes. Specificity is achieved through interactions between the N-terminal and central regions of FGFs and two loop regions in D3 that are subject to alternative splicing. These structures provide a molecular basis for FGF1 as a universal FGFR ligand and for modulation of FGF-FGFR specificity through primary sequence variations and alternative splicing.

Links

PubMed

Keywords

Amino Acid Sequence; Fibroblast Growth Factor 1; Fibroblast Growth Factor 2/chemistry; Humans; Ligands; Molecular Sequence Data; Protein Binding; Protein Conformation; Receptors, Fibroblast Growth Factor/chemistry; Signal Transduction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:FGF1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P11362

F

Seeded From UniProt

complete

HUMAN:FGF2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P21802

F

Seeded From UniProt

complete

HUMAN:FGFR1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P05230

F

Seeded From UniProt

complete

HUMAN:FGFR2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P09038

F

Seeded From UniProt

complete

HUMAN:FGF1

involved_in

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P11362

P

Seeded From UniProt

complete

HUMAN:FGF1

enables

GO:0005104: fibroblast growth factor receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P11362

F

Seeded From UniProt

complete

HUMAN:FGFR1

involved_in

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P61148

P

Seeded From UniProt

complete

HUMAN:FGFR2

enables

GO:0005007: fibroblast growth factor-activated receptor activity

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P09038

F

Seeded From UniProt

complete

HUMAN:FGFR2

involved_in

GO:0008543: fibroblast growth factor receptor signaling pathway

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P09038

P

Seeded From UniProt

complete


See also

References

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