Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats
O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recogniz...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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The Royal Society
2017-01-01
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| Series: | Open Biology |
| Subjects: | |
| Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170078 |
| _version_ | 1818967434222108672 |
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| author | Karim Rafie Olawale Raimi Andrew T. Ferenbach Vladimir S. Borodkin Vaibhav Kapuria Daan M. F. van Aalten |
| author_facet | Karim Rafie Olawale Raimi Andrew T. Ferenbach Vladimir S. Borodkin Vaibhav Kapuria Daan M. F. van Aalten |
| author_sort | Karim Rafie |
| collection | DOAJ |
| description | O-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site. |
| first_indexed | 2024-12-20T13:48:44Z |
| format | Article |
| id | doaj.art-21a9f124fabb4a7cbe3a2df051cdbdb9 |
| institution | Directory Open Access Journal |
| issn | 2046-2441 |
| language | English |
| last_indexed | 2024-12-20T13:48:44Z |
| publishDate | 2017-01-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj.art-21a9f124fabb4a7cbe3a2df051cdbdb92022-12-21T19:38:35ZengThe Royal SocietyOpen Biology2046-24412017-01-017610.1098/rsob.170078170078Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeatsKarim RafieOlawale RaimiAndrew T. FerenbachVladimir S. BorodkinVaibhav KapuriaDaan M. F. van AaltenO-linked N-acetylglucosamine (O-GlcNAc) is an essential and dynamic post-translational modification found on hundreds of nucleocytoplasmic proteins in metazoa. Although a single enzyme, O-GlcNAc transferase (OGT), generates the entire cytosolic O-GlcNAc proteome, it is not understood how it recognizes its protein substrates, targeting only a fraction of serines/threonines in the metazoan proteome for glycosylation. We describe a trapped complex of human OGT with the C-terminal domain of TAB1, a key innate immunity-signalling O-GlcNAc protein, revealing extensive interactions with the tetratricopeptide repeats of OGT. Confirmed by mutagenesis, this interaction suggests that glycosylation substrate specificity is achieved by recognition of a degenerate sequon in the active site combined with an extended conformation C-terminal of the O-GlcNAc target site.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170078glycosylationsignallingo-glcnaco-glcnac transferasesubstrate recognition |
| spellingShingle | Karim Rafie Olawale Raimi Andrew T. Ferenbach Vladimir S. Borodkin Vaibhav Kapuria Daan M. F. van Aalten Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats Open Biology glycosylation signalling o-glcnac o-glcnac transferase substrate recognition |
| title | Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats |
| title_full | Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats |
| title_fullStr | Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats |
| title_full_unstemmed | Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats |
| title_short | Recognition of a glycosylation substrate by the O-GlcNAc transferase TPR repeats |
| title_sort | recognition of a glycosylation substrate by the o glcnac transferase tpr repeats |
| topic | glycosylation signalling o-glcnac o-glcnac transferase substrate recognition |
| url | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170078 |
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