An Alternative Pin1 Binding and Isomerization Site in the N-Terminus Domain of PSD-95
Phosphorylation-dependent peptidyl-prolyl cis-trans isomerization plays key roles in cell cycle progression, the pathogenesis of cancer, and age-related neurodegeneration. Most of our knowledge about the role of phosphorylation-dependent peptidyl-prolyl cis-trans isomerization and the enzyme catalyz...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2020.00031/full |
| _version_ | 1818293986994946048 |
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| author | Jary Y. Delgado |
| author_facet | Jary Y. Delgado |
| author_sort | Jary Y. Delgado |
| collection | DOAJ |
| description | Phosphorylation-dependent peptidyl-prolyl cis-trans isomerization plays key roles in cell cycle progression, the pathogenesis of cancer, and age-related neurodegeneration. Most of our knowledge about the role of phosphorylation-dependent peptidyl-prolyl cis-trans isomerization and the enzyme catalyzing this reaction, the peptidyl-prolyl isomerase (Pin1), is largely limited to proteins not present in neurons. Only a handful of examples have shown that phosphorylation-dependent peptidyl-prolyl cis-trans isomerization, Pin1 binding, or Pin1-mediated peptidyl-prolyl cis-trans isomerization regulate proteins present at excitatory synapses. In this work, I confirm previous findings showing that Pin1 binds postsynaptic density protein-95 (PSD-95) and identify an alternative binding site in the phosphorylated N-terminus of the PSD-95. Pin1 associates via its WW domain with phosphorylated threonine (T19) and serine (S25) in the N-terminus domain of PSD-95 and this association alters the local conformation of PSD-95. Most importantly, I show that proline-directed phosphorylation of the N-terminus domain of PSD-95 alters the local conformation of this region. Therefore, proline-directed phosphorylation of the N-terminus of PSD-95, Pin1 association, and peptidyl-prolyl cis-trans isomerization may all play a role in excitatory synaptic function and synapse development. |
| first_indexed | 2024-12-13T03:24:35Z |
| format | Article |
| id | doaj.art-4be78e048b7f437087d2a8cd202da34e |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-13T03:24:35Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-4be78e048b7f437087d2a8cd202da34e2022-12-22T00:01:18ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992020-03-011310.3389/fnmol.2020.00031501124An Alternative Pin1 Binding and Isomerization Site in the N-Terminus Domain of PSD-95Jary Y. DelgadoPhosphorylation-dependent peptidyl-prolyl cis-trans isomerization plays key roles in cell cycle progression, the pathogenesis of cancer, and age-related neurodegeneration. Most of our knowledge about the role of phosphorylation-dependent peptidyl-prolyl cis-trans isomerization and the enzyme catalyzing this reaction, the peptidyl-prolyl isomerase (Pin1), is largely limited to proteins not present in neurons. Only a handful of examples have shown that phosphorylation-dependent peptidyl-prolyl cis-trans isomerization, Pin1 binding, or Pin1-mediated peptidyl-prolyl cis-trans isomerization regulate proteins present at excitatory synapses. In this work, I confirm previous findings showing that Pin1 binds postsynaptic density protein-95 (PSD-95) and identify an alternative binding site in the phosphorylated N-terminus of the PSD-95. Pin1 associates via its WW domain with phosphorylated threonine (T19) and serine (S25) in the N-terminus domain of PSD-95 and this association alters the local conformation of PSD-95. Most importantly, I show that proline-directed phosphorylation of the N-terminus domain of PSD-95 alters the local conformation of this region. Therefore, proline-directed phosphorylation of the N-terminus of PSD-95, Pin1 association, and peptidyl-prolyl cis-trans isomerization may all play a role in excitatory synaptic function and synapse development.https://www.frontiersin.org/article/10.3389/fnmol.2020.00031/fullpostsynaptic density protein 95proline-directed phosphorylationexcitatory synaptic transmissionPin1cis-trans isomerization |
| spellingShingle | Jary Y. Delgado An Alternative Pin1 Binding and Isomerization Site in the N-Terminus Domain of PSD-95 Frontiers in Molecular Neuroscience postsynaptic density protein 95 proline-directed phosphorylation excitatory synaptic transmission Pin1 cis-trans isomerization |
| title | An Alternative Pin1 Binding and Isomerization Site in the N-Terminus Domain of PSD-95 |
| title_full | An Alternative Pin1 Binding and Isomerization Site in the N-Terminus Domain of PSD-95 |
| title_fullStr | An Alternative Pin1 Binding and Isomerization Site in the N-Terminus Domain of PSD-95 |
| title_full_unstemmed | An Alternative Pin1 Binding and Isomerization Site in the N-Terminus Domain of PSD-95 |
| title_short | An Alternative Pin1 Binding and Isomerization Site in the N-Terminus Domain of PSD-95 |
| title_sort | alternative pin1 binding and isomerization site in the n terminus domain of psd 95 |
| topic | postsynaptic density protein 95 proline-directed phosphorylation excitatory synaptic transmission Pin1 cis-trans isomerization |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2020.00031/full |
| work_keys_str_mv | AT jaryydelgado analternativepin1bindingandisomerizationsiteinthenterminusdomainofpsd95 AT jaryydelgado alternativepin1bindingandisomerizationsiteinthenterminusdomainofpsd95 |