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A genome-wide study of PDZ-domain interactions in C. elegans reveals a high frequency of non-canonical binding

BACKGROUND: Proteins may evolve through the recruitment and modification of discrete domains, and in many cases, protein action can be dissected at the domain level. PDZ domains are found in many important structural and signaling complexes, and are generally thought to interact with their protein p...

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Autores principales: Lenfant, Nicolas, Polanowska, Jolanta, Bamps, Sophie, Omi, Shizue, Borg, Jean-Paul, Reboul, Jérôme
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091786/
https://www.ncbi.nlm.nih.gov/pubmed/21110867
http://dx.doi.org/10.1186/1471-2164-11-671
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author Lenfant, Nicolas
Polanowska, Jolanta
Bamps, Sophie
Omi, Shizue
Borg, Jean-Paul
Reboul, Jérôme
author_facet Lenfant, Nicolas
Polanowska, Jolanta
Bamps, Sophie
Omi, Shizue
Borg, Jean-Paul
Reboul, Jérôme
author_sort Lenfant, Nicolas
collection PubMed
description BACKGROUND: Proteins may evolve through the recruitment and modification of discrete domains, and in many cases, protein action can be dissected at the domain level. PDZ domains are found in many important structural and signaling complexes, and are generally thought to interact with their protein partners through a C-terminal consensus sequence. We undertook a comprehensive search for protein partners of all individual PDZ domains in C. elegans to characterize their function and mode of interaction. RESULTS: Coupling high-throughput yeast two-hybrid screens with extensive validation by co-affinity purification, we defined a domain-orientated interactome map. This integrates PDZ domain proteins in numerous cell-signaling pathways and shows that PDZ domain proteins are implicated in an unexpectedly wide range of cellular processes. Importantly, we uncovered a high frequency of non-canonical interactions, not involving the C-terminus of the protein partner, which were directly confirmed in most cases. We completed our study with the generation of a yeast array representing the entire set of PDZ domains from C. elegans and provide a proof-of-principle for its application to the discovery of PDZ domain targets for any protein or peptide of interest. CONCLUSIONS: We provide an extensive domain-centered dataset, together with a clone resource, that will help future functional study of PDZ domains. Through this unbiased approach, we revealed frequent non-canonical interactions between PDZ domains and their protein partners that will require a re-evaluation of this domain's molecular function. [The protein interactions from this publication have been submitted to the IMEx (http://www.imexconsortium.org) consortium through IntAct (PMID: 19850723) and assigned the identifier IM-14654]
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spelling pubmed-30917862011-05-11 A genome-wide study of PDZ-domain interactions in C. elegans reveals a high frequency of non-canonical binding Lenfant, Nicolas Polanowska, Jolanta Bamps, Sophie Omi, Shizue Borg, Jean-Paul Reboul, Jérôme BMC Genomics Research Article BACKGROUND: Proteins may evolve through the recruitment and modification of discrete domains, and in many cases, protein action can be dissected at the domain level. PDZ domains are found in many important structural and signaling complexes, and are generally thought to interact with their protein partners through a C-terminal consensus sequence. We undertook a comprehensive search for protein partners of all individual PDZ domains in C. elegans to characterize their function and mode of interaction. RESULTS: Coupling high-throughput yeast two-hybrid screens with extensive validation by co-affinity purification, we defined a domain-orientated interactome map. This integrates PDZ domain proteins in numerous cell-signaling pathways and shows that PDZ domain proteins are implicated in an unexpectedly wide range of cellular processes. Importantly, we uncovered a high frequency of non-canonical interactions, not involving the C-terminus of the protein partner, which were directly confirmed in most cases. We completed our study with the generation of a yeast array representing the entire set of PDZ domains from C. elegans and provide a proof-of-principle for its application to the discovery of PDZ domain targets for any protein or peptide of interest. CONCLUSIONS: We provide an extensive domain-centered dataset, together with a clone resource, that will help future functional study of PDZ domains. Through this unbiased approach, we revealed frequent non-canonical interactions between PDZ domains and their protein partners that will require a re-evaluation of this domain's molecular function. [The protein interactions from this publication have been submitted to the IMEx (http://www.imexconsortium.org) consortium through IntAct (PMID: 19850723) and assigned the identifier IM-14654] BioMed Central 2010-11-26 /pmc/articles/PMC3091786/ /pubmed/21110867 http://dx.doi.org/10.1186/1471-2164-11-671 Text en Copyright ©2010 Lenfant et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<url>http://creativecommons.org/licenses/by/2.0</url>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lenfant, Nicolas
Polanowska, Jolanta
Bamps, Sophie
Omi, Shizue
Borg, Jean-Paul
Reboul, Jérôme
A genome-wide study of PDZ-domain interactions in C. elegans reveals a high frequency of non-canonical binding
title A genome-wide study of PDZ-domain interactions in C. elegans reveals a high frequency of non-canonical binding
title_full A genome-wide study of PDZ-domain interactions in C. elegans reveals a high frequency of non-canonical binding
title_fullStr A genome-wide study of PDZ-domain interactions in C. elegans reveals a high frequency of non-canonical binding
title_full_unstemmed A genome-wide study of PDZ-domain interactions in C. elegans reveals a high frequency of non-canonical binding
title_short A genome-wide study of PDZ-domain interactions in C. elegans reveals a high frequency of non-canonical binding
title_sort genome-wide study of pdz-domain interactions in c. elegans reveals a high frequency of non-canonical binding
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091786/
https://www.ncbi.nlm.nih.gov/pubmed/21110867
http://dx.doi.org/10.1186/1471-2164-11-671
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