Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization.

By Joseph Schlessinger, A. Plotnikov, O. Ibrahimi, A. V. Eliseenkova, Brian K. Yeh, A. Yayon, Robert J. Linhardt, M. Mohammadi. 2000

1,193 citations recorded by the source corpus.

Subfields: Cell Biology, Genetics, Molecular Biology

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In Cell Biology

1. Xinhua Lin
2. Ding Xu
3. M. Lemmon
4. G. Schultz
5. J. Esko
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7. Csilla A. Pataki
8. J. Couchman

In Genetics

1. Xinhua Lin
2. J. Esko
3. Z. Du
4. Christine Lovly

In Molecular Biology

1. Ding Xu
2. Xinhua Lin
3. M. Lemmon
4. D. Leahy
5. Hyun-soo Cho
6. J. Esko
7. Csilla A. Pataki
8. Z. Du

Citations in the corpus

• Functions of heparan sulfate proteoglycans in cell signaling during development (2004, background): “O sulfation of HS is required for FGF1-FGFR2 and FGF2FGFR1 interactions (Pellegrini et al., 2000; Schlessinger et al., 2000).”
• Structural basis for fibroblast growth factor receptor activation. (2005, neutral): “8A) [133].”
• The FGF family: biology, pathophysiology and therapy (2009, neutral): “After the binding of ligand and HSGAGs, FGFRs dimeriz”
• An Introduction to Proteoglycans and Their Localization (2012, background): “Many members of this large family bind heparan sulfate, and crystallographic studies reveal how the FGF/HS complex interacts with the FGF receptor (FGFR) kinases (Pellegrini et al. 2000; Schlessinger et al. 2000).”
• Roles of heparan-sulphate glycosaminoglycans in cancer (2002, background): “motif within an HSGAG oligosaccharide chain, as observed by crystal-structure analysis of several protein–HSGAG complexes, including FGF1, FGF2 and ANTITHROMBIN III (AT-III”
• EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization. (2003, background): “Similarly, fibroblast growth factor University of Pennsylvania School of Medicine (FGF) receptor dimerization involves simultaneous interPhiladelphia, Pennsylvania 19104 action of FGF•heparin complexes with two receptor 3 Department of Biophysics and Biophysical Chemistry molecules (Schlessinger et ”
• Basement membranes: cell scaffoldings and signaling platforms. (2011, neutral): “In the case of the FGF receptors that bind FGF2 and that have been crystallized as a complex, formation of an active complex has been found to be greatly facilitated by heparin and heparan sulfates that interact with both FGF and receptor (Schlessinger et al. 2000).”
• FGF/FGFR signaling in health and disease (2020, background): “HSPGs. HSPGs are glycoproteins, containing one or more covalently attached heparan sulfate (HS) chains.”
• Interactions between extracellular matrix and growth factors in wound healing (2009, background): “cule bound, are linked and stabilized by heparin in a tetrameric complex.(39) FGF, fibroblast growth factor.”
• Riding the DUBway: regulation of protein trafficking by deubiquitylating enzymes (2006, neutral): “Mitochondria, for instance, regulate several facets of cellular energetics beyond ATP production , at least some through local oxidant production.”
• Mechanisms underlying differential responses to FGF signaling. (2005, background): “Furthermore, the FGF:FGFR interaction also requires the intervention of heparin or heparin sulfate proteoglycans (HSPG) that bind both the ligand and the receptor at specific domains and stabilize the formation of a receptor dimer bound to the FGF molecules [15,16].”
• Demystifying Heparan Sulfate–Protein Interactions (2014, background): “For instance, FGFR1 contains seven basic residues in an area of 350 Å2 (per monomer) but has a Kd of only 3 μM (96), whereas RAGE has seven basic residues in an area of 525 Å2 but has a Kd of ∼3 nM) (54).”
• The Structure of Glycosaminoglycans and their Interactions with Proteins (2008, background): “In the highresolution X-ray crystal structure of a 2:2:2 dimeric ternary complex of bFGF, FGFR1 and a heparin decasaccharide, heparin makes numerous contacts with both bFGF and FGFR-1, stabilising the FGF-FGFR interaction (128).”