Open AccessContrasting 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
Author(s) -
Andrew J. Borgert,
B. Lachele Foley,
David Live
Publication year - 2020
Publication title -
glycobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.757
H-Index - 128
eISSN - 1460-2423
pISSN - 0959-6658
DOI - 10.1093/glycob/cwaa112
Subject(s) - glycoconjugate , chemistry , threonine , mucin , glycoprotein , glycan , sequence (biology) , peptide , context (archaeology) , hydrogen bond , biochemistry , biophysics , glycosylation , stereochemistry , biology , enzyme , molecule , organic chemistry , paleontology , serine
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.