TY - JOUR
T1 - Structural basis for FGF receptor dimerization and activation
AU - Plotnikov, Alexander N.
AU - Schlessinger, Joseph
AU - Hubbard, Stevan R.
AU - Mohammadi, Moosa
N1 - Funding Information:
We thank A. V. Eliseenkova for production of the FGF2 and D23 in E. coli; C. Ogata for synchrotron beamline assistance; and J. Till for manuscript comments. S. R. H. is a recipient of a Kimmel Scholar Award from the Sidney Kimmel Foundation for Cancer Research. Beamline X-4A at the National Synchrotron Light Source, a DOE facility, is supported by the Howard Hughes Medical Institute.
PY - 1999/9/3
Y1 - 1999/9/3
N2 - The crystal structure of FGF2 bound to a naturally occurring variant of FGF receptor 1 (FGFR1) consisting of immunoglobulin-like domains 2 (D2) and 3 (D3) has been determined at 2.8 Δ resolution. Two FGF2:FGFR1 complexes form a 2-fold symmetric dimer. Within each complex, FGF2 interacts extensively with D2 and D3 as well as with the linker between the two domains. The dimer is stabilized by interactions between FGF2 and D2 of the adjoining complex and by a direct interaction between D2 of each receptor. A positively charged canyon formed by a cluster of exposed basic residues likely represents the heparin-binding site. A general model for FGF- and heparin-induced FGFR dimerization is inferred from the crystal structure, unifying a wealth of biochemical data.
AB - The crystal structure of FGF2 bound to a naturally occurring variant of FGF receptor 1 (FGFR1) consisting of immunoglobulin-like domains 2 (D2) and 3 (D3) has been determined at 2.8 Δ resolution. Two FGF2:FGFR1 complexes form a 2-fold symmetric dimer. Within each complex, FGF2 interacts extensively with D2 and D3 as well as with the linker between the two domains. The dimer is stabilized by interactions between FGF2 and D2 of the adjoining complex and by a direct interaction between D2 of each receptor. A positively charged canyon formed by a cluster of exposed basic residues likely represents the heparin-binding site. A general model for FGF- and heparin-induced FGFR dimerization is inferred from the crystal structure, unifying a wealth of biochemical data.
UR - http://www.scopus.com/inward/record.url?scp=0033520472&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(00)80051-3
DO - 10.1016/S0092-8674(00)80051-3
M3 - Article
C2 - 10490103
AN - SCOPUS:0033520472
SN - 0092-8674
VL - 98
SP - 641
EP - 650
JO - Cell
JF - Cell
IS - 5
ER -