title: OGlcNAcylation and phosphorylation have similar structural effects in α-helices: post-translational modifications as inducible start and stop signals in α-helices, with greater structural effects on threonine modification.
abstract: OGlcNAcylation and phosphorylation are the major competing intracellular post-translational modifications of serine and threonine residues. The structural effects of both post-translational modifications on serine and threonine were examined within Baldwin model α-helical peptides (Ac-AKAAAAKAAAAKAAGY-NH2 or Ac-YGAKAAAAKAAAAKAA-NH2). At the N-terminus of an α-helix, both phosphorylation and OGlcNAcylation stabilized the α-helix relative to the free hydroxyls, with a larger induced structure for phosphorylation than for OGlcNAcylation, for the dianionic phosphate than for the monoanionic phosphate, and for modifications on threonine than for modifications on serine. Both phosphoserine and phosphothreonine resulted in peptides more α-helical than alanine at the N-terminus, with dianionic phosphothreonine the most α-helix-stabilizing residue here. In contrast, in the interior of the α-helix, both post-translational modifications were destabilizing with respect to the α-helix, with the greatest destabilization seen for threonine OGlcNAcylation at residue 5 and threonine phosphorylation at residue 10, with peptides containing either post-translational modification existing as random coils. At the C-terminus, both OGlcNAcylation and phosphorylation were destabilizing with respect to the α-helix, though the induced structural changes were less than in the interior of the α-helix. In general, the structural effects of modifications on threonine were greater than the effects on serine, because of both the lower α-helical propensity of Thr and the more defined induced structures upon modification of threonine than serine, suggesting threonine residues are particularly important loci for structural effects of post-translational modifications. The effects of serine and threonine post-translational modifications are analogous to the effects of proline on α-helices, with the effects of phosphothreonine being greater than those of proline throughout the α-helix. These results provide a basis for understanding the context-dependent structural effects of these competing protein post-translational modifications.
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Elbaum
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Zondlo
mesh_terms: D000215:Acylation; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D005944:Glucosamine / Q000378:metabolism*; D008968:Molecular Conformation; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D013912:Threonine / Q000378:metabolism*
chemical_list: D013912:Threonine; D005944:Glucosamine