TY - JOUR
T1 - Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity
AU - Plotnikov, Alexander N.
AU - Hubbard, Stevan R.
AU - Schlessinger, Joseph
AU - Mohammadi, Moosa
N1 - Funding Information:
We thank A. V. Eliseenkova for excellent technical assistance, C. Ogata for synchrotron beamline assistance, T. Cardozo for help in homology modeling, and B. K. Yeh for help in figure preparation. S. R. H. is a recipient of a Kimmel Scholar Award from the Sidney Kimmel Foundation for Cancer Research. Beamline X4A at the National Synchrotron Light Source, a Department of Energy facility, is supported by the Howard Hughes Medical Institute. Coordinates will be deposited in the Protein Data Bank.
PY - 2000/5/12
Y1 - 2000/5/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0034640103
U2 - 10.1016/S0092-8674(00)80851-X
DO - 10.1016/S0092-8674(00)80851-X
M3 - Article
C2 - 10830168
AN - SCOPUS:0034640103
SN - 0092-8674
VL - 101
SP - 413
EP - 424
JO - Cell
JF - Cell
IS - 4
ER -