Analysis of Procollagen C-Proteinase Enhancer-1/Glycosaminoglycan Binding Sites and of the Potential Role of Calcium Ions in the Interaction

• Published in: International journal of molecular sciences Vol. 20; no. 20; p. 5021
• Main Authors: Potthoff, Jan, Bojarski, Krzysztof K, Kohut, Gergely, Lipska, Agnieszka G, Liwo, Adam, Kessler, Efrat, Ricard-Blum, Sylvie, Samsonov, Sergey A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10-10-2019; MDPI
• Subjects: Amino Acid Sequence; Binding Sites; Calcium; Calcium - chemistry; Calcium ions; Chemokines; Chondroitin sulfate; computational analysis of protein-glycosaminoglycan interactions; Computer applications; Disaccharides; Experiments; Extracellular matrix; Extracellular Matrix Proteins - chemistry; Extracellular Matrix Proteins - metabolism; fragment-based docking; Glycosaminoglycans; Glycosaminoglycans - chemistry; Glycosaminoglycans - metabolism; Growth factors; Heparan sulfate; Ions; Localization; Matrix protein; Models, Molecular; Molecular Docking Simulation; Molecular modelling; Oligosaccharides; Polysaccharides; Procollagen; procollagen c-proteinase enhancer-1; Protein Conformation; Protein interaction; Protein Interaction Domains and Motifs; Proteinase; Proteins; Structural models; Sulfation; Surface plasmon resonance; glycosaminoglycans; calcium ions; computational analysis of protein-glycosaminoglycan interactions; procollagen C-proteinase enhancer-1; fragment-based docking
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20205021

In this study, we characterize the interactions between the extracellular matrix protein, procollagen C-proteinase enhancer-1 (PCPE-1), and glycosaminoglycans (GAGs), which are linear anionic periodic polysaccharides. We applied molecular modeling approaches to build a structural model of full-length PCPE-1, which is not experimentally available, to predict GAG binding poses for various GAG lengths, types and sulfation patterns, and to determine the effect of calcium ions on the binding. The computational data are analyzed and discussed in the context of the experimental results previously obtained using surface plasmon resonance binding assays. We also provide experimental data on PCPE-1/GAG interactions obtained using inhibition assays with GAG oligosaccharides ranging from disaccharides to octadecasaccharides. Our results predict the localization of GAG-binding sites at the amino acid residue level onto PCPE-1 and is the first attempt to describe the effects of ions on protein-GAG binding using modeling approaches. In addition, this study allows us to get deeper insights into the in silico methodology challenges and limitations when applied to GAG-protein interactions.