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Mapping the heparin‐binding site of the osteoinductive protein NELL1 by site‐directed mutagenesis
Author(s) -
Takahashi Kaneyoshi,
Imai Arisa,
Iijima Masumi,
Yoshimoto Nobuo,
Maturana Andrés D.,
Kuroda Shun'ichi,
Niimi Tomoaki
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.11.032
Subject(s) - binding site , von willebrand factor , thrombospondin , binding domain , microbiology and biotechnology , chemistry , plasma protein binding , biochemistry , heparin , biology , platelet , enzyme , immunology , metalloproteinase
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.