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Science 23 February 1996:
Vol. 271. no. 5252, pp. 1116 - 1120
DOI: 10.1126/science.271.5252.1116
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Reports

Heparin Structure and Interactions with Basic Fibroblast Growth Factor

S. Faham, R. E. Hileman, J. R. Fromm, R. J. Linhardt, (1) D. C. Rees (1)

Crystal structures of heparin-derived tetra- and hexasaccharides complexed with basic fibroblast growth factor (bFGF) were determined at resolutions of 1.9 and 2.2 angstroms, respectively. The heparin structure may be approximated as a helical polymer with a disaccharide rotation of 174° and a translation of 8.6 angstroms along the helix axis. Both molecules bound similarly to a region of the bFGF surface containing residues asparagine-28, arginine-121, lysine-126, and glutamine-135; the hexasaccharide also interacted with an additional binding site formed by lysine-27, asparagine-102, and lysine-136. No significant conformational change in bFGF occurred upon heparin oligosaccharide binding, which suggests that heparin primarily serves to juxtapose components of the FGF signal transduction pathway.

S. Faham and D. C. Rees, Division of Chemistry and Chemical Engineering 147-75CH, California Institute of Technology, Pasadena, CA 91125, USA.
R. E. Hileman, J. R. Fromm, R. J. Linhardt, Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA.
(1) To whom correspondence should be addressed. E-mail: rees{at}citray.caltech.edu and linhardt{at}blue.weeg.uiowa.edu


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J. Biol. Chem. 273, 10914-10918
   Abstract »    Full Text »    PDF »
Molecular Characterization and Expression of Heparan-sulfate 6-Sulfotransferase. COMPLETE cDNA CLONING IN HUMAN AND PARTIAL CLONING IN CHINESE HAMSTER OVARY CELLS.
H. Habuchi, M. Kobayashi, and K. Kimata (1998)
J. Biol. Chem. 273, 9208-9213
   Abstract »    Full Text »    PDF »
Identification of the Second Heparin-Binding Domain in Human Complement Factor H.
T. K. Blackmore, J. Hellwage, T. A. Sadlon, N. Higgs, P. F. Zipfel, H. M. Ward, and D. L. Gordon (1998)
J. Immunol. 160, 3342-3348
   Abstract »    Full Text »    PDF »
Interaction of Heparan Sulfate from Mammary Cells with Acidic Fibroblast Growth Factor (FGF) and Basic FGF. REGULATION OF THE ACTIVITY OF BASIC FGF BY HIGH AND LOW AFFINITY BINDING SITES IN HEPARAN SULFATE.
H. Rahmoune, H.-L. Chen, J. T. Gallagher, P. S. Rudland, and D. G. Fernig (1998)
J. Biol. Chem. 273, 7303-7310
   Abstract »    Full Text »    PDF »
Molecular Modeling of Ligand and Mutation Sites of the Type A Domains of Human von Willebrand Factor and Their Relevance to von Willebrand's Disease.
P. V. Jenkins, K. J. Pasi, and S. J. Perkins (1998)
Blood 91, 2032-2044
   Abstract »    Full Text »    PDF »
Interaction between Pseudorabies Virus and Heparin/Heparan Sulfate. PSEUDORABIES VIRUS MUTANTS DIFFER IN THEIR INTERACTION WITH HEPARIN/HEPARAN SULFATE WHEN ALTERED FOR SPECIFIC GLYCOPROTEIN C HEPARIN-BINDING DOMAIN.
E. Trybala, T. Bergstrom, D. Spillmann, B. Svennerholm, S. J. Flynn, and P. Ryan (1998)
J. Biol. Chem. 273, 5047-5052
   Abstract »    Full Text »    PDF »
Identification of Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) as the Rosetting Ligand of the Malaria Parasite P. falciparum.
Q. Chen, A. Barragan, V. Fernandez, A. Sundstrom, M. Schlichtherle, A. Sahlen, J. Carlson, S. Datta, and M. Wahlgren (1998)
J. Exp. Med. 187, 15-23
   Abstract »    Full Text »    PDF »
Hepatocyte Growth Factor/Scatter Factor Binds with High Affinity to Dermatan Sulfate.
M. Lyon, J. A. Deakin, H. Rahmoune, D. G. Fernig, T. Nakamura, and J. T. Gallagher (1998)
J. Biol. Chem. 273, 271-278
   Abstract »    Full Text »    PDF »
Structural Requirement of Heparan Sulfate for Interaction with Herpes Simplex Virus Type 1 Virions and Isolated Glycoprotein C.
E. Feyzi, E. Trybala, T. Bergstrom, U. Lindahl, and D. Spillmann (1997)
J. Biol. Chem. 272, 24850-24857
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The Interaction of the Transforming Growth Factor-beta s with Heparin/Heparan Sulfate Is Isoform-specific.
M. Lyon, G. Rushton, and J. T. Gallagher (1997)
J. Biol. Chem. 272, 18000-18006
   Abstract »    Full Text »    PDF »
Heparin-induced Self-association of Fibroblast Growth Factor-2. EVIDENCE FOR TWO OLIGOMERIZATION PROCESSES.
A. B. Herr, D. M. Ornitz, R. Sasisekharan, G. Venkataraman, and G. Waksman (1997)
J. Biol. Chem. 272, 16382-16389
   Abstract »    Full Text »    PDF »
Analysis of Binding of Cobra Cardiotoxins to Heparin Reveals a New beta -Sheet Heparin-binding Structural Motif.
A. A. Vyas, J.-J. Pan, H. V. Patel, K. A. Vyas, C.-M. Chiang, Y.-C. Sheu, J.-K. Hwang, and W.-g. Wu (1997)
J. Biol. Chem. 272, 9661-9670
   Abstract »    Full Text »    PDF »
Interaction of Heparin with Human Angiogenin.
F. Soncin, D. J. Strydom, and R. Shapiro (1997)
J. Biol. Chem. 272, 9818-9824
   Abstract »    Full Text »    PDF »
Identification of a Glycosaminoglycan-binding Site in Chemokine Macrophage Inflammatory Protein-1alpha.
W. Koopmann and M. S. Krangel (1997)
J. Biol. Chem. 272, 10103-10109
   Abstract »    Full Text »    PDF »


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