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

Authors
Schlessinger, Joseph
Plotnikov, Alexander N.
Ibrahimi, Omar A.
Eliseenkova, Anna V.
Yeh, Brian K.
Yayon, Avner
Linhardt, Robert J.
Mohammadi, Moosa
ORCID
https://orcid.org/0000-0003-2219-5833
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Other Contributors
Issue Date
2000-01-01
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
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Full Citation
Crystal Structure of a Ternary FGF-FGFR-Heparin Complex Reveals a Dual Role for Heparin in FGFR Binding and Dimerization, J. Schlessinger, A.N. Plotnikov, O.A. Ibrahimi, A.V. Eliseenkova, B.K. Yeh, A. Yayon, R.J. Linhardt, M. Mohammadi, Molecular Cell, 6, 743-750, 2000.
Abstract
The crystal structure of a dimeric 2:2:2 FGF:FGFR:heparin ternary complex at 3 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.
Description
Molecular Cell, 6, 743-750
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Molecular Cell
https://harc.rpi.edu/
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