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Mapping the heparin-binding site of the osteoinductive protein NELL1 by site-directed mutagenesis
- Takahashi, Kaneyoshi, Imai, Arisa, Iijima, Masumi, Yoshimoto, Nobuo, Maturana, Andrés D., Kuroda, Shun’ichi, Niimi, Tomoaki
- FEBS letters 2015 v.589 pp. 4026-4032
- blood coagulation factors, models, mutants, proteoglycans, site-directed mutagenesis
- 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.