1. Heparin-Promoted Cellular Uptake of the Cell-Penetrating Glycosaminoglycan Binding Peptide, GBPECP, Depends on a Single Tryptophan
- Author
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Ping-Hsieh Kuo, Shih-Che Sue, Jia-Yin Lu, Chien-Jung Chen, Ingjye Jiang, Yi-Lin Hung, Li-Chun Hung, Margaret Dah-Tsyr Chang, Yi-Fen Hsieh, and Lily Hui-Ching Wang
- Subjects
0301 basic medicine ,chemistry.chemical_classification ,Glycan ,Glycosaminoglycan binding ,030102 biochemistry & molecular biology ,biology ,Peptide ,General Medicine ,Heparin ,Plasma protein binding ,Biochemistry ,Micelle ,03 medical and health sciences ,Residue (chemistry) ,030104 developmental biology ,chemistry ,biology.protein ,medicine ,Molecular Medicine ,Binding site ,medicine.drug - Abstract
A 10-residue, glycosaminoglycan-binding peptide, GBPECP, derived from human eosinophil cationic protein has been recently designated as a potent cell-penetrating peptide. A model system containing peptide, glycan, and lipid was monitored by nuclear magnetic resonance (NMR) spectroscopy to determine the cell-penetrating mechanism. Heparin octasaccharide with dodecylphosphocholine (DPC) lipid micelle was titrated into the GBPECP solution. Our data revealed substantial roles for the charged residues Arg5 and Lys7 in recognizing heparin, whereas Arg3 had less effect. The aromatic residue Trp4 acted as an irreplaceable moiety for membrane insertion, as the replacement of Trp4 with Arg4 abolished cell penetration, although it significantly improved the heparin-binding ability. GBPECP bound either heparin or lipid in the presence or absence of the other ligand indicating that the peptide has two alternative binding sites: Trp4 is responsible for lipid insertion, and Arg5 and Lys7 are for GAG binding. We develope...
- Published
- 2016
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