In silico investigation of Alsin RLD conformational dynamics and phosphoinositides binding mechanism.
Alsin is a protein known for its major role in neuronal homeostasis and whose mutation is associated with early-onset neurodegenerative diseases. It has been shown that its relocalization from the cytoplasm to the cell membrane is crucial to induce early endosomes maturation. In particular, evidence...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0270955 |
| _version_ | 1811223128943099904 |
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| author | Marco Cannariato Marcello Miceli Marco Agostino Deriu |
| author_facet | Marco Cannariato Marcello Miceli Marco Agostino Deriu |
| author_sort | Marco Cannariato |
| collection | DOAJ |
| description | Alsin is a protein known for its major role in neuronal homeostasis and whose mutation is associated with early-onset neurodegenerative diseases. It has been shown that its relocalization from the cytoplasm to the cell membrane is crucial to induce early endosomes maturation. In particular, evidences suggest that the N-terminal regulator of chromosome condensation 1 like domain (RLD) is necessary for membrane association thanks to its affinity to phosphoinositides, membrane lipids involved in the regulation of several signaling processes. Interestingly, this domain showed affinity towards phosphatidylinositol 3-phosphate [PI(3)P], which is highly expressed in endosomes membrane. However, Alsin structure has not been experimentally resolved yet and molecular mechanisms associated with its biological functions are mostly unknown. In this work, Alsin RLD has been investigated through computational molecular modeling techniques to analyze its conformational dynamics and obtain a representative 3D model of this domain. Moreover, a putative phosphoinositide binding site has been proposed and PI(3)P interaction mechanism studied. Results highlight the substantial conformational stability of Alsin RLD secondary structure and suggest the role of one highly flexible region in the phosphoinositides selectivity of this domain. |
| first_indexed | 2024-04-12T08:26:37Z |
| format | Article |
| id | doaj.art-aa3c506cf6874719935a23387347c1a4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T08:26:37Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-aa3c506cf6874719935a23387347c1a42022-12-22T03:40:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01177e027095510.1371/journal.pone.0270955In silico investigation of Alsin RLD conformational dynamics and phosphoinositides binding mechanism.Marco CannariatoMarcello MiceliMarco Agostino DeriuAlsin is a protein known for its major role in neuronal homeostasis and whose mutation is associated with early-onset neurodegenerative diseases. It has been shown that its relocalization from the cytoplasm to the cell membrane is crucial to induce early endosomes maturation. In particular, evidences suggest that the N-terminal regulator of chromosome condensation 1 like domain (RLD) is necessary for membrane association thanks to its affinity to phosphoinositides, membrane lipids involved in the regulation of several signaling processes. Interestingly, this domain showed affinity towards phosphatidylinositol 3-phosphate [PI(3)P], which is highly expressed in endosomes membrane. However, Alsin structure has not been experimentally resolved yet and molecular mechanisms associated with its biological functions are mostly unknown. In this work, Alsin RLD has been investigated through computational molecular modeling techniques to analyze its conformational dynamics and obtain a representative 3D model of this domain. Moreover, a putative phosphoinositide binding site has been proposed and PI(3)P interaction mechanism studied. Results highlight the substantial conformational stability of Alsin RLD secondary structure and suggest the role of one highly flexible region in the phosphoinositides selectivity of this domain.https://doi.org/10.1371/journal.pone.0270955 |
| spellingShingle | Marco Cannariato Marcello Miceli Marco Agostino Deriu In silico investigation of Alsin RLD conformational dynamics and phosphoinositides binding mechanism. PLoS ONE |
| title | In silico investigation of Alsin RLD conformational dynamics and phosphoinositides binding mechanism. |
| title_full | In silico investigation of Alsin RLD conformational dynamics and phosphoinositides binding mechanism. |
| title_fullStr | In silico investigation of Alsin RLD conformational dynamics and phosphoinositides binding mechanism. |
| title_full_unstemmed | In silico investigation of Alsin RLD conformational dynamics and phosphoinositides binding mechanism. |
| title_short | In silico investigation of Alsin RLD conformational dynamics and phosphoinositides binding mechanism. |
| title_sort | in silico investigation of alsin rld conformational dynamics and phosphoinositides binding mechanism |
| url | https://doi.org/10.1371/journal.pone.0270955 |
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