Enzymatic Phosphorylation of Ser in a Type I Collagen Peptide
| Autor: | Yu-Shan Lin, Erik Poppleton, Hongtao Yu, Sandra E. Wiley, Yimin Qiu, Sourav Banerjee, Barbara Brodsky, David L. Kaplan, Jack E. Dixon, Arya Mekkat |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Protein Conformation alpha-Helical Protein Folding Biophysics Peptide Molecular Dynamics Simulation Collagen Type I 03 medical and health sciences 0302 clinical medicine Protein structure Serine Amino Acid Sequence Phosphorylation Protein kinase A Peptide sequence chemistry.chemical_classification Mitogen-Activated Protein Kinase 3 Kinase Protein Stability Phosphoproteomics Proteins Peptide Fragments 030104 developmental biology chemistry 030217 neurology & neurosurgery Type I collagen |
| Zdroj: | Biophysical journal. 115(12) |
| ISSN: | 1542-0086 |
| Popis: | Phosphoproteomics studies have reported phosphorylation at multiple sites within collagen, raising the possibility that these post-translational modifications regulate the physical or biological properties of collagen. In this study, molecular dynamics simulations and experimental studies were carried out on model peptides to establish foundational principles of phosphorylation of Ser residues in collagen. A (Gly-Xaa-Yaa)11 peptide was designed to include a Ser-containing sequence from type I collagen that was reported to be phosphorylated. The physiological kinase involved in collagen phosphorylation is not known. In vitro studies showed that a model kinase ERK1 (extracellular signal-regulated protein kinase 1) would phosphorylate Ser within the consensus sequence if the collagen-like peptide is in the denatured state but not in the triple-helical state. The peptide was not a substrate for FAM20C, a kinase present in the secretory pathway, which has been shown to phosphorylate many extracellular matrix proteins. The unfolded single chain (Gly-Xaa-Yaa)11 peptide containing phosphoSer was able to refold to form a stable triple helix but at a reduced folding rate and with a small decrease in thermal stability relative to the nonphosphorylated peptide at neutral pH. These biophysical studies on model peptides provide a basis for investigations into the physiological consequences of collagen phosphorylation and the application of phosphorylation to regulate the properties of collagen biomaterials. |
| Databáze: | OpenAIRE |
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