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Systematic Discovery of New Recognition Peptides Mediating Protein Interaction Networks
Many aspects of cell signalling, trafficking, and targeting are governed by interactions between globular protein domains and short peptide segments. These domains often bind multiple peptides that share a common sequence pattern, or “linear motif” (e.g., SH3 binding to PxxP). Many domains are known...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1283537/ https://www.ncbi.nlm.nih.gov/pubmed/16279839 http://dx.doi.org/10.1371/journal.pbio.0030405 |
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author | Neduva, Victor Linding, Rune Su-Angrand, Isabelle Stark, Alexander de Masi, Federico Gibson, Toby J Lewis, Joe Serrano, Luis Russell, Robert B |
author_facet | Neduva, Victor Linding, Rune Su-Angrand, Isabelle Stark, Alexander de Masi, Federico Gibson, Toby J Lewis, Joe Serrano, Luis Russell, Robert B |
author_sort | Neduva, Victor |
collection | PubMed |
description | Many aspects of cell signalling, trafficking, and targeting are governed by interactions between globular protein domains and short peptide segments. These domains often bind multiple peptides that share a common sequence pattern, or “linear motif” (e.g., SH3 binding to PxxP). Many domains are known, though comparatively few linear motifs have been discovered. Their short length (three to eight residues), and the fact that they often reside in disordered regions in proteins makes them difficult to detect through sequence comparison or experiment. Nevertheless, each new motif provides critical molecular details of how interaction networks are constructed, and can explain how one protein is able to bind to very different partners. Here we show that binding motifs can be detected using data from genome-scale interaction studies, and thus avoid the normally slow discovery process. Our approach based on motif over-representation in non-homologous sequences, rediscovers known motifs and predicts dozens of others. Direct binding experiments reveal that two predicted motifs are indeed protein-binding modules: a DxxDxxxD protein phosphatase 1 binding motif with a K (D) of 22 μM and a VxxxRxYS motif that binds Translin with a K (D) of 43 μM. We estimate that there are dozens or even hundreds of linear motifs yet to be discovered that will give molecular insight into protein networks and greatly illuminate cellular processes. |
format | Text |
id | pubmed-1283537 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-12835372005-11-15 Systematic Discovery of New Recognition Peptides Mediating Protein Interaction Networks Neduva, Victor Linding, Rune Su-Angrand, Isabelle Stark, Alexander de Masi, Federico Gibson, Toby J Lewis, Joe Serrano, Luis Russell, Robert B PLoS Biol Research Article Many aspects of cell signalling, trafficking, and targeting are governed by interactions between globular protein domains and short peptide segments. These domains often bind multiple peptides that share a common sequence pattern, or “linear motif” (e.g., SH3 binding to PxxP). Many domains are known, though comparatively few linear motifs have been discovered. Their short length (three to eight residues), and the fact that they often reside in disordered regions in proteins makes them difficult to detect through sequence comparison or experiment. Nevertheless, each new motif provides critical molecular details of how interaction networks are constructed, and can explain how one protein is able to bind to very different partners. Here we show that binding motifs can be detected using data from genome-scale interaction studies, and thus avoid the normally slow discovery process. Our approach based on motif over-representation in non-homologous sequences, rediscovers known motifs and predicts dozens of others. Direct binding experiments reveal that two predicted motifs are indeed protein-binding modules: a DxxDxxxD protein phosphatase 1 binding motif with a K (D) of 22 μM and a VxxxRxYS motif that binds Translin with a K (D) of 43 μM. We estimate that there are dozens or even hundreds of linear motifs yet to be discovered that will give molecular insight into protein networks and greatly illuminate cellular processes. Public Library of Science 2005-12 2005-11-15 /pmc/articles/PMC1283537/ /pubmed/16279839 http://dx.doi.org/10.1371/journal.pbio.0030405 Text en Copyright: © 2005 Neduva 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 Neduva, Victor Linding, Rune Su-Angrand, Isabelle Stark, Alexander de Masi, Federico Gibson, Toby J Lewis, Joe Serrano, Luis Russell, Robert B Systematic Discovery of New Recognition Peptides Mediating Protein Interaction Networks |
title | Systematic Discovery of New Recognition Peptides Mediating Protein Interaction Networks |
title_full | Systematic Discovery of New Recognition Peptides Mediating Protein Interaction Networks |
title_fullStr | Systematic Discovery of New Recognition Peptides Mediating Protein Interaction Networks |
title_full_unstemmed | Systematic Discovery of New Recognition Peptides Mediating Protein Interaction Networks |
title_short | Systematic Discovery of New Recognition Peptides Mediating Protein Interaction Networks |
title_sort | systematic discovery of new recognition peptides mediating protein interaction networks |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1283537/ https://www.ncbi.nlm.nih.gov/pubmed/16279839 http://dx.doi.org/10.1371/journal.pbio.0030405 |
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