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A Dynamic View of Domain-Motif Interactions
Many protein-protein interactions are mediated by domain-motif interaction, where a domain in one protein binds a short linear motif in its interacting partner. Such interactions are often involved in key cellular processes, necessitating their tight regulation. A common strategy of the cell to cont...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257277/ https://www.ncbi.nlm.nih.gov/pubmed/22253583 http://dx.doi.org/10.1371/journal.pcbi.1002341 |
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author | Akiva, Eyal Friedlander, Gilgi Itzhaki, Zohar Margalit, Hanah |
author_facet | Akiva, Eyal Friedlander, Gilgi Itzhaki, Zohar Margalit, Hanah |
author_sort | Akiva, Eyal |
collection | PubMed |
description | Many protein-protein interactions are mediated by domain-motif interaction, where a domain in one protein binds a short linear motif in its interacting partner. Such interactions are often involved in key cellular processes, necessitating their tight regulation. A common strategy of the cell to control protein function and interaction is by post-translational modifications of specific residues, especially phosphorylation. Indeed, there are motifs, such as SH2-binding motifs, in which motif phosphorylation is required for the domain-motif interaction. On the contrary, there are other examples where motif phosphorylation prevents the domain-motif interaction. Here we present a large-scale integrative analysis of experimental human data of domain-motif interactions and phosphorylation events, demonstrating an intriguing coupling between the two. We report such coupling for SH3, PDZ, SH2 and WW domains, where residue phosphorylation within or next to the motif is implied to be associated with switching on or off domain binding. For domains that require motif phosphorylation for binding, such as SH2 domains, we found coupled phosphorylation events other than the ones required for domain binding. Furthermore, we show that phosphorylation might function as a double switch, concurrently enabling interaction of the motif with one domain and disabling interaction with another domain. Evolutionary analysis shows that co-evolution of the motif and the proximal residues capable of phosphorylation predominates over other evolutionary scenarios, in which the motif appeared before the potentially phosphorylated residue, or vice versa. Our findings provide strengthening evidence for coupled interaction-regulation units, defined by a domain-binding motif and a phosphorylated residue. |
format | Online Article Text |
id | pubmed-3257277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32572772012-01-17 A Dynamic View of Domain-Motif Interactions Akiva, Eyal Friedlander, Gilgi Itzhaki, Zohar Margalit, Hanah PLoS Comput Biol Research Article Many protein-protein interactions are mediated by domain-motif interaction, where a domain in one protein binds a short linear motif in its interacting partner. Such interactions are often involved in key cellular processes, necessitating their tight regulation. A common strategy of the cell to control protein function and interaction is by post-translational modifications of specific residues, especially phosphorylation. Indeed, there are motifs, such as SH2-binding motifs, in which motif phosphorylation is required for the domain-motif interaction. On the contrary, there are other examples where motif phosphorylation prevents the domain-motif interaction. Here we present a large-scale integrative analysis of experimental human data of domain-motif interactions and phosphorylation events, demonstrating an intriguing coupling between the two. We report such coupling for SH3, PDZ, SH2 and WW domains, where residue phosphorylation within or next to the motif is implied to be associated with switching on or off domain binding. For domains that require motif phosphorylation for binding, such as SH2 domains, we found coupled phosphorylation events other than the ones required for domain binding. Furthermore, we show that phosphorylation might function as a double switch, concurrently enabling interaction of the motif with one domain and disabling interaction with another domain. Evolutionary analysis shows that co-evolution of the motif and the proximal residues capable of phosphorylation predominates over other evolutionary scenarios, in which the motif appeared before the potentially phosphorylated residue, or vice versa. Our findings provide strengthening evidence for coupled interaction-regulation units, defined by a domain-binding motif and a phosphorylated residue. Public Library of Science 2012-01-12 /pmc/articles/PMC3257277/ /pubmed/22253583 http://dx.doi.org/10.1371/journal.pcbi.1002341 Text en Akiva et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Akiva, Eyal Friedlander, Gilgi Itzhaki, Zohar Margalit, Hanah A Dynamic View of Domain-Motif Interactions |
title | A Dynamic View of Domain-Motif Interactions |
title_full | A Dynamic View of Domain-Motif Interactions |
title_fullStr | A Dynamic View of Domain-Motif Interactions |
title_full_unstemmed | A Dynamic View of Domain-Motif Interactions |
title_short | A Dynamic View of Domain-Motif Interactions |
title_sort | dynamic view of domain-motif interactions |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257277/ https://www.ncbi.nlm.nih.gov/pubmed/22253583 http://dx.doi.org/10.1371/journal.pcbi.1002341 |
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