Crystal Structure of a Ternary FGF-FGFR-Heparin Complex Reveals a Dual Role for Heparin in FGFR Binding and Dimerization Export

@article{citeulike:2731354, abstract = {The crystal structure of a dimeric 2:2:2 FGF:FGFR:heparin ternary complex at 3 \r{A} resolution has been determined. Within each 1:1 FGF:FGFR complex, heparin makes numerous contacts with both FGF and FGFR, thereby augmenting FGF-FGFR binding. Heparin also interacts with FGFR in the adjoining 1:1 FGF:FGFR complex to promote FGFR dimerization. The 6-O-sulfate group of heparin plays a pivotal role in mediating both interactions. The unexpected stoichiometry of heparin binding in the structure led us to propose a revised model for FGFR dimerization. Biochemical data in support of this model are also presented. This model provides a structural basis for FGFR activation by small molecule heparin analogs and may facilitate the design of heparin mimetics capable of modulating FGF signaling.}, author = {Schlessinger, J.}, citeulike-article-id = {2731354}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/S1097-2765(00)00073-3}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S1097-2765(00)00073-3}, citeulike-linkout-2 = {http://www.sciencedirect.com/science/article/B6WSR-41FKPV5-V/1/dd17519112f15e877d20ba9a46c2af57}, doi = {10.1016/S1097-2765(00)00073-3}, issn = {10972765}, journal = {Molecular Cell}, keywords = {fgf, fgfr, h, heparin, structure, t}, month = {September}, number = {3}, pages = {743--750}, posted-at = {2009-09-22 23:06:24}, priority = {2}, title = {Crystal Structure of a Ternary FGF-FGFR-Heparin Complex Reveals a Dual Role for Heparin in FGFR Binding and Dimerization}, url = {http://dx.doi.org/10.1016/S1097-2765(00)00073-3}, volume = {6}, year = {2000} }

TY - JOUR ID - citeulike:2731354 L3 - citeulike-article-id:2731354 N2 - The crystal structure of a dimeric 2:2:2 FGF:FGFR:heparin ternary complex at 3 Å resolution has been determined. Within each 1:1 FGF:FGFR complex, heparin makes numerous contacts with both FGF and FGFR, thereby augmenting FGF-FGFR binding. Heparin also interacts with FGFR in the adjoining 1:1 FGF:FGFR complex to promote FGFR dimerization. The 6-O-sulfate group of heparin plays a pivotal role in mediating both interactions. The unexpected stoichiometry of heparin binding in the structure led us to propose a revised model for FGFR dimerization. Biochemical data in support of this model are also presented. This model provides a structural basis for FGFR activation by small molecule heparin analogs and may facilitate the design of heparin mimetics capable of modulating FGF signaling. IS - 3 JF - Molecular Cell SN - 10972765 EP - 750 TI - Crystal Structure of a Ternary FGF-FGFR-Heparin Complex Reveals a Dual Role for Heparin in FGFR Binding and Dimerization VL - 6 SP - 743 KW - fgf KW - fgfr KW - h KW - heparin KW - structure KW - t AU - Schlessinger, J PY - 2000/09// UR - http://dx.doi.org/10.1016/S1097-2765(00)00073-3 ER -