Conformational changes of GDNF-derived peptide induced by heparin, heparan sulfate, and sulfated hyaluronic acid - Analysis by circular dichroism spectroscopy and molecular dynamics simulation.

Lakkoji Satish, Santanu Santra, Mikhail V Tsurkan, Carsten Werner, Madhurima Jana, Harekrushna Sahoo

Journal: International journal of biological macromolecules 2021;182():2144-2150

PMID: 34087306

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: Biophysical and Protein Chemistry Laboratory, Department of Chemistry, National Institute of Technology Rourkela, Odisha 769008, India; School of Chemical Sciences, National Institute of Science Education and Research, HBNI, Bhubaneswar, Odisha 752050, India.; Molecular Simulation Laboratory, Department of Chemistry, National Institute of Technology Rourkela, Odisha 769008, India.; Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, 01069 Dresden, Germany; Center for Regenerative Therapies Dresden, Technische Universität Dresden, 01307 Dresden, Germany.; Biophysical and Protein Chemistry Laboratory, Department of Chemistry, National Institute of Technology Rourkela, Odisha 769008, India; Center for Nanomaterials, National Institute of Technology Rourkela, Odisha 769008, India. Electronic address: [email protected].

DOI: 10.1016/j.ijbiomac.2021.05.194

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MeSH Terms: Amino Acid Sequence, Circular Dichroism, Glial Cell Line-Derived Neurotrophic Factor, Heparin, Heparitin Sulfate, Hyaluronic Acid, Molecular Dynamics Simulation, Peptides, Protein Conformation, Solvents, Time Factors