Proteome-level assessment of origin, prevalence and function of leucine-aspartic acid (LD) motifs
<h3>Motivation</h3><p dir="ltr">Leucine-aspartic acid (LD) motifs are short linear interaction motifs (SLiMs) that link paxillin family proteins to factors controlling cell adhesion, motility and survival. The existence and importance of LD motifs beyond the paxillin fami...
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2019
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| _version_ | 1864513512755167232 |
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| author | Tanvir Alam (638619) |
| author2 | Meshari Alazmi (452881) Rayan Naser (18812002) Franceline Huser (18812005) Afaque A Momin (18812008) Veronica Astro (217791) SeungBeom Hong (18812011) Katarzyna W Walkiewicz (18812014) Christian G Canlas (18812017) Raphaël Huser (810533) Amal J Ali (18812020) Jasmeen Merzaban (777475) Antonio Adamo (1619932) Mariusz Jaremko (363140) Łukasz Jaremko (363141) Vladimir B Bajic (18812023) Xin Gao (14001) Stefan T Arold (15448526) |
| author2_role | author author author author author author author author author author author author author author author author author |
| author_facet | Tanvir Alam (638619) Meshari Alazmi (452881) Rayan Naser (18812002) Franceline Huser (18812005) Afaque A Momin (18812008) Veronica Astro (217791) SeungBeom Hong (18812011) Katarzyna W Walkiewicz (18812014) Christian G Canlas (18812017) Raphaël Huser (810533) Amal J Ali (18812020) Jasmeen Merzaban (777475) Antonio Adamo (1619932) Mariusz Jaremko (363140) Łukasz Jaremko (363141) Vladimir B Bajic (18812023) Xin Gao (14001) Stefan T Arold (15448526) |
| author_role | author |
| dc.creator.none.fl_str_mv | Tanvir Alam (638619) Meshari Alazmi (452881) Rayan Naser (18812002) Franceline Huser (18812005) Afaque A Momin (18812008) Veronica Astro (217791) SeungBeom Hong (18812011) Katarzyna W Walkiewicz (18812014) Christian G Canlas (18812017) Raphaël Huser (810533) Amal J Ali (18812020) Jasmeen Merzaban (777475) Antonio Adamo (1619932) Mariusz Jaremko (363140) Łukasz Jaremko (363141) Vladimir B Bajic (18812023) Xin Gao (14001) Stefan T Arold (15448526) |
| dc.date.none.fl_str_mv | 2019-10-04T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1093/bioinformatics/btz703 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Proteome-level_assessment_of_origin_prevalence_and_function_of_leucine-aspartic_acid_LD_motifs/26022304 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Bioinformatics and computational biology Information and computing sciences Data management and data science Leucine-aspartic acid motifs LD motifs, short linear interaction motifs (SLiMs) cell adhesion motility paxillin family proteins computational predictions experimental validation |
| dc.title.none.fl_str_mv | Proteome-level assessment of origin, prevalence and function of leucine-aspartic acid (LD) motifs |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Motivation</h3><p dir="ltr">Leucine-aspartic acid (LD) motifs are short linear interaction motifs (SLiMs) that link paxillin family proteins to factors controlling cell adhesion, motility and survival. The existence and importance of LD motifs beyond the paxillin family is poorly understood.</p><h3>Results</h3><p dir="ltr">To enable a proteome-wide assessment of LD motifs, we developed an active learning based framework (LD motif finder; LDMF) that iteratively integrates computational predictions with experimental validation. Our analysis of the human proteome revealed a dozen new proteins containing LD motifs. We found that LD motif signalling evolved in unicellular eukaryotes more than 800 Myr ago, with paxillin and vinculin as core constituents, and nuclear export signal as a likely source of de novo LD motifs. We show that LD motif proteins form a functionally homogenous group, all being involved in cell morphogenesis and adhesion. This functional focus is recapitulated in cells by GFP-fused LD motifs, suggesting that it is intrinsic to the LD motif sequence, possibly through their effect on binding partners. Our approach elucidated the origin and dynamic adaptations of an ancestral SLiM, and can serve as a guide for the identification of other SLiMs for which only few representatives are known.</p><h2>Other Information</h2><p dir="ltr">Published in: Bioinformatics<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1093/bioinformatics/btz703" target="_blank">https://dx.doi.org/10.1093/bioinformatics/btz703</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_aa79d72e735c3f50f293db1b8c0098f1 |
| identifier_str_mv | 10.1093/bioinformatics/btz703 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26022304 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Proteome-level assessment of origin, prevalence and function of leucine-aspartic acid (LD) motifsTanvir Alam (638619)Meshari Alazmi (452881)Rayan Naser (18812002)Franceline Huser (18812005)Afaque A Momin (18812008)Veronica Astro (217791)SeungBeom Hong (18812011)Katarzyna W Walkiewicz (18812014)Christian G Canlas (18812017)Raphaël Huser (810533)Amal J Ali (18812020)Jasmeen Merzaban (777475)Antonio Adamo (1619932)Mariusz Jaremko (363140)Łukasz Jaremko (363141)Vladimir B Bajic (18812023)Xin Gao (14001)Stefan T Arold (15448526)Biological sciencesBiochemistry and cell biologyBioinformatics and computational biologyInformation and computing sciencesData management and data scienceLeucine-aspartic acid motifsLD motifs, short linear interaction motifs (SLiMs)cell adhesionmotilitypaxillin family proteinscomputational predictionsexperimental validation<h3>Motivation</h3><p dir="ltr">Leucine-aspartic acid (LD) motifs are short linear interaction motifs (SLiMs) that link paxillin family proteins to factors controlling cell adhesion, motility and survival. The existence and importance of LD motifs beyond the paxillin family is poorly understood.</p><h3>Results</h3><p dir="ltr">To enable a proteome-wide assessment of LD motifs, we developed an active learning based framework (LD motif finder; LDMF) that iteratively integrates computational predictions with experimental validation. Our analysis of the human proteome revealed a dozen new proteins containing LD motifs. We found that LD motif signalling evolved in unicellular eukaryotes more than 800 Myr ago, with paxillin and vinculin as core constituents, and nuclear export signal as a likely source of de novo LD motifs. We show that LD motif proteins form a functionally homogenous group, all being involved in cell morphogenesis and adhesion. This functional focus is recapitulated in cells by GFP-fused LD motifs, suggesting that it is intrinsic to the LD motif sequence, possibly through their effect on binding partners. Our approach elucidated the origin and dynamic adaptations of an ancestral SLiM, and can serve as a guide for the identification of other SLiMs for which only few representatives are known.</p><h2>Other Information</h2><p dir="ltr">Published in: Bioinformatics<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1093/bioinformatics/btz703" target="_blank">https://dx.doi.org/10.1093/bioinformatics/btz703</a></p>2019-10-04T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1093/bioinformatics/btz703https://figshare.com/articles/journal_contribution/Proteome-level_assessment_of_origin_prevalence_and_function_of_leucine-aspartic_acid_LD_motifs/26022304CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/260223042019-10-04T03:00:00Z |
| spellingShingle | Proteome-level assessment of origin, prevalence and function of leucine-aspartic acid (LD) motifs Tanvir Alam (638619) Biological sciences Biochemistry and cell biology Bioinformatics and computational biology Information and computing sciences Data management and data science Leucine-aspartic acid motifs LD motifs, short linear interaction motifs (SLiMs) cell adhesion motility paxillin family proteins computational predictions experimental validation |
| status_str | publishedVersion |
| title | Proteome-level assessment of origin, prevalence and function of leucine-aspartic acid (LD) motifs |
| title_full | Proteome-level assessment of origin, prevalence and function of leucine-aspartic acid (LD) motifs |
| title_fullStr | Proteome-level assessment of origin, prevalence and function of leucine-aspartic acid (LD) motifs |
| title_full_unstemmed | Proteome-level assessment of origin, prevalence and function of leucine-aspartic acid (LD) motifs |
| title_short | Proteome-level assessment of origin, prevalence and function of leucine-aspartic acid (LD) motifs |
| title_sort | Proteome-level assessment of origin, prevalence and function of leucine-aspartic acid (LD) motifs |
| topic | Biological sciences Biochemistry and cell biology Bioinformatics and computational biology Information and computing sciences Data management and data science Leucine-aspartic acid motifs LD motifs, short linear interaction motifs (SLiMs) cell adhesion motility paxillin family proteins computational predictions experimental validation |