Novel linear motif filtering protocol reveals the role of the LC8 dynein light chain in the Hippo pathway.
Protein-protein interactions (PPIs) formed between short linear motifs and globular domains play important roles in many regulatory and signaling processes but are highly underrepresented in current protein-protein interaction databases. These types of interactions are usually characterized by a spe...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-12-01
|
| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC5746249?pdf=render |
| _version_ | 1818278665475063808 |
|---|---|
| author | Gábor Erdős Tamás Szaniszló Mátyás Pajkos Borbála Hajdu-Soltész Bence Kiss Gábor Pál László Nyitray Zsuzsanna Dosztányi |
| author_facet | Gábor Erdős Tamás Szaniszló Mátyás Pajkos Borbála Hajdu-Soltész Bence Kiss Gábor Pál László Nyitray Zsuzsanna Dosztányi |
| author_sort | Gábor Erdős |
| collection | DOAJ |
| description | Protein-protein interactions (PPIs) formed between short linear motifs and globular domains play important roles in many regulatory and signaling processes but are highly underrepresented in current protein-protein interaction databases. These types of interactions are usually characterized by a specific binding motif that captures the key amino acids shared among the interaction partners. However, the computational proteome-level identification of interaction partners based on the known motif is hindered by the huge number of randomly occurring matches from which biologically relevant motif hits need to be extracted. In this work, we established a novel bioinformatic filtering protocol to efficiently explore interaction network of a hub protein. We introduced a novel measure that enabled the optimization of the elements and parameter settings of the pipeline which was built from multiple sequence-based prediction methods. In addition, data collected from PPI databases and evolutionary analyses were also incorporated to further increase the biological relevance of the identified motif hits. The approach was applied to the dynein light chain LC8, a ubiquitous eukaryotic hub protein that has been suggested to be involved in motor-related functions as well as promoting the dimerization of various proteins by recognizing linear motifs in its partners. From the list of putative binding motifs collected by our protocol, several novel peptides were experimentally verified to bind LC8. Altogether 71 potential new motif instances were identified. The expanded list of LC8 binding partners revealed the evolutionary plasticity of binding partners despite the highly conserved binding interface. In addition, it also highlighted a novel, conserved function of LC8 in the upstream regulation of the Hippo signaling pathway. Beyond the LC8 system, our work also provides general guidelines that can be applied to explore the interaction network of other linear motif binding proteins or protein domains. |
| first_indexed | 2024-12-12T23:21:03Z |
| format | Article |
| id | doaj.art-9f72bfccb1c34b449303a0b6a11bca49 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-12T23:21:03Z |
| publishDate | 2017-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-9f72bfccb1c34b449303a0b6a11bca492022-12-22T00:08:17ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582017-12-011312e100588510.1371/journal.pcbi.1005885Novel linear motif filtering protocol reveals the role of the LC8 dynein light chain in the Hippo pathway.Gábor ErdősTamás SzaniszlóMátyás PajkosBorbála Hajdu-SoltészBence KissGábor PálLászló NyitrayZsuzsanna DosztányiProtein-protein interactions (PPIs) formed between short linear motifs and globular domains play important roles in many regulatory and signaling processes but are highly underrepresented in current protein-protein interaction databases. These types of interactions are usually characterized by a specific binding motif that captures the key amino acids shared among the interaction partners. However, the computational proteome-level identification of interaction partners based on the known motif is hindered by the huge number of randomly occurring matches from which biologically relevant motif hits need to be extracted. In this work, we established a novel bioinformatic filtering protocol to efficiently explore interaction network of a hub protein. We introduced a novel measure that enabled the optimization of the elements and parameter settings of the pipeline which was built from multiple sequence-based prediction methods. In addition, data collected from PPI databases and evolutionary analyses were also incorporated to further increase the biological relevance of the identified motif hits. The approach was applied to the dynein light chain LC8, a ubiquitous eukaryotic hub protein that has been suggested to be involved in motor-related functions as well as promoting the dimerization of various proteins by recognizing linear motifs in its partners. From the list of putative binding motifs collected by our protocol, several novel peptides were experimentally verified to bind LC8. Altogether 71 potential new motif instances were identified. The expanded list of LC8 binding partners revealed the evolutionary plasticity of binding partners despite the highly conserved binding interface. In addition, it also highlighted a novel, conserved function of LC8 in the upstream regulation of the Hippo signaling pathway. Beyond the LC8 system, our work also provides general guidelines that can be applied to explore the interaction network of other linear motif binding proteins or protein domains.http://europepmc.org/articles/PMC5746249?pdf=render |
| spellingShingle | Gábor Erdős Tamás Szaniszló Mátyás Pajkos Borbála Hajdu-Soltész Bence Kiss Gábor Pál László Nyitray Zsuzsanna Dosztányi Novel linear motif filtering protocol reveals the role of the LC8 dynein light chain in the Hippo pathway. PLoS Computational Biology |
| title | Novel linear motif filtering protocol reveals the role of the LC8 dynein light chain in the Hippo pathway. |
| title_full | Novel linear motif filtering protocol reveals the role of the LC8 dynein light chain in the Hippo pathway. |
| title_fullStr | Novel linear motif filtering protocol reveals the role of the LC8 dynein light chain in the Hippo pathway. |
| title_full_unstemmed | Novel linear motif filtering protocol reveals the role of the LC8 dynein light chain in the Hippo pathway. |
| title_short | Novel linear motif filtering protocol reveals the role of the LC8 dynein light chain in the Hippo pathway. |
| title_sort | novel linear motif filtering protocol reveals the role of the lc8 dynein light chain in the hippo pathway |
| url | http://europepmc.org/articles/PMC5746249?pdf=render |
| work_keys_str_mv | AT gaborerdos novellinearmotiffilteringprotocolrevealstheroleofthelc8dyneinlightchaininthehippopathway AT tamasszaniszlo novellinearmotiffilteringprotocolrevealstheroleofthelc8dyneinlightchaininthehippopathway AT matyaspajkos novellinearmotiffilteringprotocolrevealstheroleofthelc8dyneinlightchaininthehippopathway AT borbalahajdusoltesz novellinearmotiffilteringprotocolrevealstheroleofthelc8dyneinlightchaininthehippopathway AT bencekiss novellinearmotiffilteringprotocolrevealstheroleofthelc8dyneinlightchaininthehippopathway AT gaborpal novellinearmotiffilteringprotocolrevealstheroleofthelc8dyneinlightchaininthehippopathway AT laszlonyitray novellinearmotiffilteringprotocolrevealstheroleofthelc8dyneinlightchaininthehippopathway AT zsuzsannadosztanyi novellinearmotiffilteringprotocolrevealstheroleofthelc8dyneinlightchaininthehippopathway |