Conformational changes of GDNF-derived peptide induced by heparin, heparan sulfate, and sulfated hyaluronic acid – Analysis by circular dichroism spectroscopy and molecular dynamics simulation
| Autor: | Harekrushna Sahoo, Lakkoji Satish, Mikhail V. Tsurkan, Santanu Santra, Carsten Werner, Madhurima Jana |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Circular dichroism
Glycan Time Factors Protein Conformation Peptide 02 engineering and technology Molecular Dynamics Simulation Biochemistry Glycosaminoglycan 03 medical and health sciences chemistry.chemical_compound Sulfation Structural Biology Hyaluronic acid Glial cell line-derived neurotrophic factor Amino Acid Sequence Glial Cell Line-Derived Neurotrophic Factor Hyaluronic Acid Molecular Biology 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology Heparin Circular Dichroism General Medicine Heparan sulfate 021001 nanoscience & nanotechnology chemistry Solvents Biophysics biology.protein Heparitin Sulfate Peptides 0210 nano-technology |
| Zdroj: | International Journal of Biological Macromolecules. 182:2144-2150 |
| ISSN: | 0141-8130 |
| DOI: | 10.1016/j.ijbiomac.2021.05.194 |
| Popis: | Glial-cell-line-derived neurotrophic factor (GDNF) is a protein that has therapeutic potential in the treatment of Parkinson's disease and other neurodegenerative diseases. The activity of GDNF is highly dependent on the interaction with sulfated glycans which bind at the N-terminus consisting of 19 residues. Herein, we studied the influence of different glycosaminoglycan (i.e., glycan; GAG) molecules on the conformation of a GDNF-derived peptide (GAG binding motif, sixteen amino acid residues at the N-terminus) using both experimental and theoretical studies. The GAG molecules employed in this study are heparin, heparan sulfate, hyaluronic acid, and sulfated hyaluronic acid. Circular dichroism spectroscopy was employed to detect conformational changes induced by the GAG molecules; molecular dynamics simulation studies were performed to support the experimental results. Our results revealed that the sulfated GAG molecules bind strongly with GDNF peptide and induce alpha-helical structure in the peptide to some extent. |
| Databáze: | OpenAIRE |
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