Influence of nonenzymatic posttranslational modifications on constitution, oligomerization and receptor binding of S100A12.
This study examined the effect of methylglyoxal (MGO)-derived nonenzymatic posttranslational modifications (nePTMs) on the binding affinity of S100A12 to its natural receptor for advanced glycation end-products (RAGE). Binding of MGO-modified S100A12 to RAGE decreased significantly with increasing M...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0113418&type=printable |
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| author | Kerstin Augner Jutta Eichler Wolfgang Utz Monika Pischetsrieder |
| author_facet | Kerstin Augner Jutta Eichler Wolfgang Utz Monika Pischetsrieder |
| author_sort | Kerstin Augner |
| collection | DOAJ |
| description | This study examined the effect of methylglyoxal (MGO)-derived nonenzymatic posttranslational modifications (nePTMs) on the binding affinity of S100A12 to its natural receptor for advanced glycation end-products (RAGE). Binding of MGO-modified S100A12 to RAGE decreased significantly with increasing MGO concentration and incubation time. Ca(2+)-induced S100A12 hexamerization was impaired only at higher MGO concentrations indicating that the loss of affinity is not predominantly caused by disturbance of ligand oligomerization. nePTM mapping showed carboxyethylation of lysine (CEL) and the N-terminus without preferential modification sites. Besides, hydroimidazolone, hemiaminals, argpyrimidine, and tetrahydropyrimidine rapidly formed at R21. Even at the highest modification rate, hexamerization of synthesized CEL-S100A12 was unaffected and RAGE-binding only slightly impaired. Thus, nePTMs at R21 seem to be the major cause of MGO-induced impairment of S100A12 oligomerization and RAGE binding. |
| format | Article |
| id | doaj-art-e81e57a84ff14b02bebfa64a25212717 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-e81e57a84ff14b02bebfa64a252127172025-08-20T03:01:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11341810.1371/journal.pone.0113418Influence of nonenzymatic posttranslational modifications on constitution, oligomerization and receptor binding of S100A12.Kerstin AugnerJutta EichlerWolfgang UtzMonika PischetsriederThis study examined the effect of methylglyoxal (MGO)-derived nonenzymatic posttranslational modifications (nePTMs) on the binding affinity of S100A12 to its natural receptor for advanced glycation end-products (RAGE). Binding of MGO-modified S100A12 to RAGE decreased significantly with increasing MGO concentration and incubation time. Ca(2+)-induced S100A12 hexamerization was impaired only at higher MGO concentrations indicating that the loss of affinity is not predominantly caused by disturbance of ligand oligomerization. nePTM mapping showed carboxyethylation of lysine (CEL) and the N-terminus without preferential modification sites. Besides, hydroimidazolone, hemiaminals, argpyrimidine, and tetrahydropyrimidine rapidly formed at R21. Even at the highest modification rate, hexamerization of synthesized CEL-S100A12 was unaffected and RAGE-binding only slightly impaired. Thus, nePTMs at R21 seem to be the major cause of MGO-induced impairment of S100A12 oligomerization and RAGE binding.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0113418&type=printable |
| spellingShingle | Kerstin Augner Jutta Eichler Wolfgang Utz Monika Pischetsrieder Influence of nonenzymatic posttranslational modifications on constitution, oligomerization and receptor binding of S100A12. PLoS ONE |
| title | Influence of nonenzymatic posttranslational modifications on constitution, oligomerization and receptor binding of S100A12. |
| title_full | Influence of nonenzymatic posttranslational modifications on constitution, oligomerization and receptor binding of S100A12. |
| title_fullStr | Influence of nonenzymatic posttranslational modifications on constitution, oligomerization and receptor binding of S100A12. |
| title_full_unstemmed | Influence of nonenzymatic posttranslational modifications on constitution, oligomerization and receptor binding of S100A12. |
| title_short | Influence of nonenzymatic posttranslational modifications on constitution, oligomerization and receptor binding of S100A12. |
| title_sort | influence of nonenzymatic posttranslational modifications on constitution oligomerization and receptor binding of s100a12 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0113418&type=printable |
| work_keys_str_mv | AT kerstinaugner influenceofnonenzymaticposttranslationalmodificationsonconstitutionoligomerizationandreceptorbindingofs100a12 AT juttaeichler influenceofnonenzymaticposttranslationalmodificationsonconstitutionoligomerizationandreceptorbindingofs100a12 AT wolfgangutz influenceofnonenzymaticposttranslationalmodificationsonconstitutionoligomerizationandreceptorbindingofs100a12 AT monikapischetsrieder influenceofnonenzymaticposttranslationalmodificationsonconstitutionoligomerizationandreceptorbindingofs100a12 |