Mapping the heparin‐binding site of the osteoinductive protein NELL1 by site‐directed mutagenesis. Issue 24 (26th November 2015)

• Record Type: Journal Article
• Authors: Takahashi, Kaneyoshi; Imai, Arisa; Iijima, Masumi; Yoshimoto, Nobuo; Maturana, Andrés D.; Kuroda, Shun'ichi; Niimi, Tomoaki
• Is Part Of: FEBS letters. Volume 589:Issue 24(2015) Part B
• Page Start: 4026
• Page End: 4032
• Publication Date: 2015-11-26
• Subjects: DS -- dermatan sulfate -- EGF -- epidermal growth factor -- ECM -- extracellular matrix -- GAG -- glycosaminoglycan -- HS -- heparan sulfate -- HSPG -- heparan sulfate proteoglycan -- NELL1 -- neural epidermal growth factor-like (NEL)-like 1 -- OVA -- ovalbumin -- TSP -- thrombospondin -- TSPN -- N-terminal thrombospondin-1-like -- VWC -- von Willebrand factor type C -- Heparin-binding -- Heparan sulfate proteoglycan -- Neural epidermal growth factor-like (NEL)-like 1 -- Thrombospondin -- TSPN domain; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2015.11.032
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract : NELL1 interacts with cell surface HSPGs through its N‐terminal TSPN domain. The apparent Kd for the interaction of NELL1 for immobilized heparin was ∼400 nM. Five basic residues, Arg 107, Arg 122, Arg 126, Arg 193 and Lys 196, bind heparin.