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Evolutionarily conserved bias of amino-acid usage refines the definition of PDZ-binding motif

BACKGROUND: The interactions between PDZ (PSD-95, Dlg, ZO-1) domains and PDZ-binding motifs play central roles in signal transductions within cells. Proteins with PDZ domains bind to PDZ-binding motifs almost exclusively when the motifs are located at the carboxyl (C-) terminal ends of their binding...

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Autores principales: Chimura, Takahiko, Launey, Thomas, Ito, Masao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138430/
https://www.ncbi.nlm.nih.gov/pubmed/21649932
http://dx.doi.org/10.1186/1471-2164-12-300
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author Chimura, Takahiko
Launey, Thomas
Ito, Masao
author_facet Chimura, Takahiko
Launey, Thomas
Ito, Masao
author_sort Chimura, Takahiko
collection PubMed
description BACKGROUND: The interactions between PDZ (PSD-95, Dlg, ZO-1) domains and PDZ-binding motifs play central roles in signal transductions within cells. Proteins with PDZ domains bind to PDZ-binding motifs almost exclusively when the motifs are located at the carboxyl (C-) terminal ends of their binding partners. However, it remains little explored whether PDZ-binding motifs show any preferential location at the C-terminal ends of proteins, at genome-level. RESULTS: Here, we examined the distribution of the type-I (x-x-S/T-x-I/L/V) or type-II (x-x-V-x-I/V) PDZ-binding motifs in proteins encoded in the genomes of five different species (human, mouse, zebrafish, fruit fly and nematode). We first established that these PDZ-binding motifs are indeed preferentially present at their C-terminal ends. Moreover, we found specific amino acid (AA) bias for the 'x' positions in the motifs at the C-terminal ends. In general, hydrophilic AAs were favored. Our genomics-based findings confirm and largely extend the results of previous interaction-based studies, allowing us to propose refined consensus sequences for all of the examined PDZ-binding motifs. An ontological analysis revealed that the refined motifs are functionally relevant since a large fraction of the proteins bearing the motif appear to be involved in signal transduction. Furthermore, co-precipitation experiments confirmed two new protein interactions predicted by our genomics-based approach. Finally, we show that influenza virus pathogenicity can be correlated with PDZ-binding motif, with high-virulence viral proteins bearing a refined PDZ-binding motif. CONCLUSIONS: Our refined definition of PDZ-binding motifs should provide important clues for identifying functional PDZ-binding motifs and proteins involved in signal transduction.
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spelling pubmed-31384302011-07-19 Evolutionarily conserved bias of amino-acid usage refines the definition of PDZ-binding motif Chimura, Takahiko Launey, Thomas Ito, Masao BMC Genomics Research Article BACKGROUND: The interactions between PDZ (PSD-95, Dlg, ZO-1) domains and PDZ-binding motifs play central roles in signal transductions within cells. Proteins with PDZ domains bind to PDZ-binding motifs almost exclusively when the motifs are located at the carboxyl (C-) terminal ends of their binding partners. However, it remains little explored whether PDZ-binding motifs show any preferential location at the C-terminal ends of proteins, at genome-level. RESULTS: Here, we examined the distribution of the type-I (x-x-S/T-x-I/L/V) or type-II (x-x-V-x-I/V) PDZ-binding motifs in proteins encoded in the genomes of five different species (human, mouse, zebrafish, fruit fly and nematode). We first established that these PDZ-binding motifs are indeed preferentially present at their C-terminal ends. Moreover, we found specific amino acid (AA) bias for the 'x' positions in the motifs at the C-terminal ends. In general, hydrophilic AAs were favored. Our genomics-based findings confirm and largely extend the results of previous interaction-based studies, allowing us to propose refined consensus sequences for all of the examined PDZ-binding motifs. An ontological analysis revealed that the refined motifs are functionally relevant since a large fraction of the proteins bearing the motif appear to be involved in signal transduction. Furthermore, co-precipitation experiments confirmed two new protein interactions predicted by our genomics-based approach. Finally, we show that influenza virus pathogenicity can be correlated with PDZ-binding motif, with high-virulence viral proteins bearing a refined PDZ-binding motif. CONCLUSIONS: Our refined definition of PDZ-binding motifs should provide important clues for identifying functional PDZ-binding motifs and proteins involved in signal transduction. BioMed Central 2011-06-08 /pmc/articles/PMC3138430/ /pubmed/21649932 http://dx.doi.org/10.1186/1471-2164-12-300 Text en Copyright ©2010 Chimura et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Chimura, Takahiko
Launey, Thomas
Ito, Masao
Evolutionarily conserved bias of amino-acid usage refines the definition of PDZ-binding motif
title Evolutionarily conserved bias of amino-acid usage refines the definition of PDZ-binding motif
title_full Evolutionarily conserved bias of amino-acid usage refines the definition of PDZ-binding motif
title_fullStr Evolutionarily conserved bias of amino-acid usage refines the definition of PDZ-binding motif
title_full_unstemmed Evolutionarily conserved bias of amino-acid usage refines the definition of PDZ-binding motif
title_short Evolutionarily conserved bias of amino-acid usage refines the definition of PDZ-binding motif
title_sort evolutionarily conserved bias of amino-acid usage refines the definition of pdz-binding motif
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138430/
https://www.ncbi.nlm.nih.gov/pubmed/21649932
http://dx.doi.org/10.1186/1471-2164-12-300
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