title: Mapping the heparin-binding site of the osteoinductive protein NELL1 by site-directed mutagenesis.
abstract: Neural epidermal growth factor-like (NEL)-like 1 (NELL1) is a secretory osteogenic protein comprising an N-terminal thrombospondin-1-like (TSPN) domain, four von Willebrand factor type C domains, and six epidermal growth factor-like repeats. NELL1 shows heparin-binding activity; however, the biological significance remains to be explored. In this report, we demonstrate that NELL1 binds to cell surface proteoglycans through its TSPN domain. Major heparin-binding sites were identified on the three-dimensional structural model of the TSPN domain of NELL1. Mutant analysis of the heparin-binding sites indicated that the heparin-binding activity of the TSPN domain is involved in interaction of NELL1 with cell surface proteoglycans.
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Kaneyoshi
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Imai
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Iijima
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yoshimoto
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Andrés D
authors.initials: AD
authors.lastname: Maturana
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan; The Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan.
authors.forename: Shun'ichi
authors.initials: S
authors.lastname: Kuroda
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan. Electronic address: tniimi@agr.nagoya-u.ac.jp.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Niimi
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000378:metabolism*; D001665:Binding Sites; D002135:Calcium-Binding Proteins; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D025941:Protein Interaction Mapping; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013045:Species Specificity; D019700:Thrombospondin 1 / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D002135:Calcium-Binding Proteins; D019812:Heparan Sulfate Proteoglycans; D050505:Mutant Proteins; C104144:NELL1 protein, human; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D019700:Thrombospondin 1; D006493:Heparin
keywords: Heparan sulfate proteoglycan; Heparin-binding; Neural epidermal growth factor-like (NEL)-like 1; TSPN domain; Thrombospondin