Details

Autor(en) / Beteiligte

• Kappler, Joachim
• Franken, Sebastian
• Junghans, Ulrich
• Hoffmann, Ralf
• Linke, Thomas
• Müller, Hans Werner
• Koch, Karl-Wilhelm

Titel

Glycosaminoglycan-Binding Properties and Secondary Structure of the C-Terminus of Netrin-1

Ist Teil von

• Biochemical and biophysical research communications, 2000-05, Vol.271 (2), p.287-291

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2000

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Netrins are soluble neurite-outgrowth-promoting proteins related to the laminin B2 chain. Since these proteins and their receptor DCC (the “deleted in colorectal carcinoma” gene product) bind heparin, glycosaminoglycans may modulate their biological actions in a similar fashion as described for several other ligand-receptor systems. Here we show that a polypeptide encompassing the C-terminal cluster of basic amino acids of netrin-1 (i) adopts an α-helical conformation in water-trifluoroethanol mixtures according to circular dichroism experiments and (ii) binds electrostatically to heparin with high affinity under physiological ionic conditions (KD = 15 nM for the binding to immobilized heparin according to surface plasmon resonance, KD = 50 nM in solution as determined with isothermal titration calorimetry). These data indicate that the cluster of basic amino acids at the C-terminus of netrin-1 forms an α-helical structural element which can contribute to the glycosaminoglycan-binding activity of this neurotrophic guidance molecule.