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dc.contributor.authorYeh, Brian K.
dc.contributor.authorEliseenkova, Anna V.
dc.contributor.authorPlotnikov, Alexander N.
dc.contributor.authorGreen, David
dc.contributor.authorPinnell, Jared
dc.contributor.authorPolat, Tulay
dc.contributor.authorGritli-Linde, Amel
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorMohammadi, Moosa
dc.identifier.citationStructural Basis for Activation of Fibroblast Growth Factor Signaling by Sucrose Octasulfate, B.K. Yeh, A.V. Eliseenkova, A.N. Plotnikov, D. Green, J. Pinnell, T. Polat, A. Gritli-Linde, R.J. Linhardt, M. Mohammadi, Molecular and Cellular Biology, 22, 7184-7192, 2002.
dc.descriptionMolecular and Cellular Biology, 22, 7184-7192
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractSucrose octasulfate (SOS) is believed to stimulate fibroblast growth factor (FGF) signaling by binding and stabilizing FGFs. In this report, we show that SOS induces FGF-dependent dimerization of FGF receptors (FGFRs). The crystal structure of the dimeric FGF2-FGFR1-SOS complex at 2.6-Å resolution reveals a symmetric assemblage of two 1:1:1 FGF2-FGFR1-SOS ternary complexes. Within each ternary complex SOS binds to FGF and FGFR and thereby increases FGF-FGFR affinity. SOS also interacts with the adjoining FGFR and thereby promotes protein-protein interactions that stabilize dimerization. This structural finding is supported by the inability of selectively desulfated SOS molecules to promote receptor dimerization. Thus, we propose that SOS potentiates FGF signaling by imitating the dual role of heparin in increasing FGF-FGFR affinity and promoting receptor dimerization. Hence, the dimeric FGF-FGFR-SOS structure substantiates the recently proposed “two-end” model, by which heparin induces FGF-FGFR dimerization. Moreover, the FGF-FGFR-SOS structure provides an attractive template for the development of easily synthesized SOS-related heparin agonists and antagonists that may hold therapeutic potential.
dc.description.sponsorshipNational Heart, Lung, and Blood Institute
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofMolecular and Cellular Biology
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleStructural Basis for Activation of Fibroblast Growth Factor Signaling by Sucrose Octasulfate
dc.rights.holderIn Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)

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