Contrasting the conformational effects of α-O-GalNAc and α-O-Man glycan protein modifications and their impact on the mucin-like region of alpha-dystroglycan
| Autor: | Andrew J. Borgert, David Live, B. Lachele Foley |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Glycan
Glycoconjugate Stereochemistry Molecular Conformation Context (language use) Peptide Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences Biochemistry Regular Manuscripts 03 medical and health sciences Molecular dynamics Peptide bond Threonine Dystroglycans Nuclear Magnetic Resonance Biomolecular Glycoproteins 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology Chemistry 0104 chemical sciences biology.protein Glycoprotein Protein Processing Post-Translational |
| Zdroj: | Glycobiology |
| ISSN: | 1460-2423 |
| DOI: | 10.1093/glycob/cwaa112 |
| Popis: | We have carried out a comparative study of the conformational impact of modifications to threonine residues of either α-O-Man or α-O-GalNAc in the context of a sequence from the mucin-like region of α-dystroglycan. Both such modifications can coexist in this domain of the glycoprotein. Solution NMR experiments and molecular dynamics calculations were employed. Comparing the results for an unmodified peptide Ac- PPTTTTKKP-NH2 sequence from α-dystroglycan, and glycoconjugates with either modification on the Ts, we find that the impact of the α-O-Man modification on the peptide scaffold is quite limited, while that of the α-O-GalNAc is more profound. The results for the α-O-GalNAc glycoconjugate are consistent with what has been seen earlier in other systems. Further examination of the NMR-based structure and the MD results suggest a more extensive network of hydrogen bond interactions within the α-O-GalNAc-threonine residue than has been previously appreciated, which influences the properties of the protein backbone. The conformational effects are relevant to the mechanical properties of α-dystroglycan. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|