論文 - 詳細
| RRC ID | 18245 |
|---|---|
| 著者 | Chimura T, Launey T, Ito M. |
| タイトル | Evolutionarily conserved bias of amino-acid usage refines the definition of PDZ-binding motif. |
| ジャーナル | BMC Genomics |
| Abstract |
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. |
| 巻・号 | 12 |
| ページ | 300 |
| 公開日 | 2011-6-8 |
| DOI | 10.1186/1471-2164-12-300 |
| PII | 1471-2164-12-300 |
| PMID | 21649932 |
| PMC | PMC3138430 |
| MeSH | Amino Acid Motifs* Amino Acid Sequence Amino Acids / metabolism* Animals Evolution, Molecular* Genomics* Humans Mice Molecular Sequence Data PDZ Domains* Protein Binding Proteins / chemistry* Proteins / genetics Proteins / metabolism* Signal Transduction Species Specificity Substrate Specificity |
| IF | 3.594 |
| 引用数 | 12 |
| WOS 分野 | BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY |
| リソース情報 | |
| ヒト・動物細胞 | COS-7(RCB0539) |