A study of the structural properties of sites modified by the O-linked 6-N-acetylglucosamine transferase.
Protein O-GlcNAcylation (O-GlcNAc) is an essential post-translational modification (PTM) in higher eukaryotes. The O-linked β-N-acetylglucosamine transferase (OGT), targets specific Serines and Threonines (S/T) in intracellular proteins. However, unlike phosphorylation, fewer than 25% of known O-Glc...
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doaj-9c9d34dc046645b6a559ec78777bdffc2020-11-24T20:52:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e018440510.1371/journal.pone.0184405A study of the structural properties of sites modified by the O-linked 6-N-acetylglucosamine transferase.Thiago Britto-BorgesGeoffrey J BartonProtein O-GlcNAcylation (O-GlcNAc) is an essential post-translational modification (PTM) in higher eukaryotes. The O-linked β-N-acetylglucosamine transferase (OGT), targets specific Serines and Threonines (S/T) in intracellular proteins. However, unlike phosphorylation, fewer than 25% of known O-GlcNAc sites match a clear sequence pattern. Accordingly, the three-dimensional structures of O-GlcNAc sites were characterised to investigate the role of structure in molecular recognition. From 1,584 O-GlcNAc sites in 620 proteins, 143 were mapped to protein structures determined by X-ray crystallography. The modified S/T were 1.7 times more likely to be annotated in the REM465 field which defines missing residues in a protein structure, while 7 O-GlcNAc sites were solvent inaccessible and unlikely to be targeted by OGT. 132 sites with complete backbone atoms clustered into 10 groups, but these were indistinguishable from clusters from unmodified S/T. This suggests there is no prevalent three-dimensional motif for OGT recognition. Predicted features from the 620 proteins were compared to unmodified S/T in O-GlcNAcylated proteins and globular proteins. The Jpred4 predicted secondary structure shows that modified S/T were more likely to be coils. 5/6 methods to predict intrinsic disorder indicated O-GlcNAcylated S/T to be significantly more disordered than unmodified S/T. Although the analysis did not find a pattern in the site three-dimensional structure, it revealed the residues around the modification site are likely to be disordered and suggests a potential role of secondary structure elements in OGT site recognition.http://europepmc.org/articles/PMC5590929?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Thiago Britto-Borges Geoffrey J Barton |
spellingShingle |
Thiago Britto-Borges Geoffrey J Barton A study of the structural properties of sites modified by the O-linked 6-N-acetylglucosamine transferase. PLoS ONE |
author_facet |
Thiago Britto-Borges Geoffrey J Barton |
author_sort |
Thiago Britto-Borges |
title |
A study of the structural properties of sites modified by the O-linked 6-N-acetylglucosamine transferase. |
title_short |
A study of the structural properties of sites modified by the O-linked 6-N-acetylglucosamine transferase. |
title_full |
A study of the structural properties of sites modified by the O-linked 6-N-acetylglucosamine transferase. |
title_fullStr |
A study of the structural properties of sites modified by the O-linked 6-N-acetylglucosamine transferase. |
title_full_unstemmed |
A study of the structural properties of sites modified by the O-linked 6-N-acetylglucosamine transferase. |
title_sort |
study of the structural properties of sites modified by the o-linked 6-n-acetylglucosamine transferase. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2017-01-01 |
description |
Protein O-GlcNAcylation (O-GlcNAc) is an essential post-translational modification (PTM) in higher eukaryotes. The O-linked β-N-acetylglucosamine transferase (OGT), targets specific Serines and Threonines (S/T) in intracellular proteins. However, unlike phosphorylation, fewer than 25% of known O-GlcNAc sites match a clear sequence pattern. Accordingly, the three-dimensional structures of O-GlcNAc sites were characterised to investigate the role of structure in molecular recognition. From 1,584 O-GlcNAc sites in 620 proteins, 143 were mapped to protein structures determined by X-ray crystallography. The modified S/T were 1.7 times more likely to be annotated in the REM465 field which defines missing residues in a protein structure, while 7 O-GlcNAc sites were solvent inaccessible and unlikely to be targeted by OGT. 132 sites with complete backbone atoms clustered into 10 groups, but these were indistinguishable from clusters from unmodified S/T. This suggests there is no prevalent three-dimensional motif for OGT recognition. Predicted features from the 620 proteins were compared to unmodified S/T in O-GlcNAcylated proteins and globular proteins. The Jpred4 predicted secondary structure shows that modified S/T were more likely to be coils. 5/6 methods to predict intrinsic disorder indicated O-GlcNAcylated S/T to be significantly more disordered than unmodified S/T. Although the analysis did not find a pattern in the site three-dimensional structure, it revealed the residues around the modification site are likely to be disordered and suggests a potential role of secondary structure elements in OGT site recognition. |
url |
http://europepmc.org/articles/PMC5590929?pdf=render |
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