title: Mapping the heparin-binding site on the 13-14F3 fragment of fibronectin.
abstract: Fibronectin, a multifunctional glycoprotein of the extracellular matrix, plays a major role in cell adhesion. Various studies have revealed that the human 13th and 14th fibronectin type III domains (labeled (13)F3 and (14)F3 here) contain a heparin-binding site. Mapping of the heparin-binding sites of (13-14)F3, (13)F3, and (14)F3 by NMR chemical shift perturbation, isothermal titration calorimetry, and molecular modeling show that (13)F3 provides the dominant heparin-binding site and that the residues involved are within the first 29 amino acids of (13)F3. Predictions from earlier biochemical and modeling studies as well as the x-ray structure of (12-14)F3 were tested. It was shown that the positively charged residues that project into the solvent from the ABE face of the triple-stranded beta sheet on (13)F3 are involved in binding, but (14)F3 does not appear to contribute significantly to heparin binding.
authors.affiliation: Department of Biochemistry and Oxford Centre for Molecular Sciences, University of Oxford, South Parks Rd., Oxford OX1 3QU, United Kingdom.
authors.lastname: Sachchidanand
authors.forename: Olivier
authors.initials: O
authors.lastname: Lequin
authors.forename: David
authors.initials: D
authors.lastname: Staunton
authors.forename: Barbara
authors.initials: B
authors.lastname: Mulloy
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Forster
authors.forename: Keiichi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Iain D
authors.initials: ID
authors.lastname: Campbell
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D005353:Fibronectins / Q000737:chemistry* / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D005353:Fibronectins; D009844:Oligosaccharides; D010446:Peptide Fragments; D011994:Recombinant Proteins; D006493:Heparin