The two isoforms of Lyn display different intramolecular fuzzy complexes with the SH3 domain

The function of the intrinsically disordered Unique domain of the Src family of tyrosine kinases (SFK), where the largest differences between family members are concentrated, remains poorly understood. Recent studies in c-Src have demonstrated that the Unique region forms transient interactions, des...

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Autores: Teixeira, Joao M. C., Fuentes, Héctor, Bielskutė, Stasė, Gairí Tahull, Margarida, Zerko, Szymon, Kozminski, Wiktor, Pons Vallès, Miquel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/125625
Acceso en línea:https://hdl.handle.net/2445/125625
Access Level:acceso abierto
Palabra clave:Proteïnes quinases
Ressonància magnètica nuclear
Bioquímica
Protein kinases
Nuclear magnetic resonance
Biochemistry
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spelling The two isoforms of Lyn display different intramolecular fuzzy complexes with the SH3 domainTeixeira, Joao M. C.Fuentes, HéctorBielskutė, StasėGairí Tahull, MargaridaZerko, SzymonKozminski, WiktorPons Vallès, MiquelProteïnes quinasesRessonància magnètica nuclearBioquímicaProtein kinasesNuclear magnetic resonanceBiochemistryThe function of the intrinsically disordered Unique domain of the Src family of tyrosine kinases (SFK), where the largest differences between family members are concentrated, remains poorly understood. Recent studies in c-Src have demonstrated that the Unique region forms transient interactions, described as an intramolecular fuzzy complex, with the SH3 domain and suggested that similar complexes could be formed by other SFKs. Src and Lyn are members of a distinct subfamily of SFKs. Lyn is a key player in the immunologic response and exists in two isoforms originating from alternative splicing in the Unique domain. We have used NMR to compare the intramolecular interactions in the two isoforms and found that the alternatively spliced segment interacts specifically with the so-called RT-loop in the SH3 domain and that this interaction is abolished when a polyproline ligand binds to the SH3 domain. These results support the generality of the fuzzy complex formation in distinct subfamilies of SFKs and its physiological role, as the naturally occurring alternative splicing modulates the interactions in this complex.MDPI2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/125625Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3390/molecules23112731Molecules, 2018, vol. 23, num. 11, p. 2731https://doi.org/10.3390/molecules23112731cc-by (c) Teixeira, Joao M. C. et al., 2018http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1256252026-05-27T06:46:51Z
dc.title.none.fl_str_mv The two isoforms of Lyn display different intramolecular fuzzy complexes with the SH3 domain
title The two isoforms of Lyn display different intramolecular fuzzy complexes with the SH3 domain
spellingShingle The two isoforms of Lyn display different intramolecular fuzzy complexes with the SH3 domain
Teixeira, Joao M. C.
Proteïnes quinases
Ressonància magnètica nuclear
Bioquímica
Protein kinases
Nuclear magnetic resonance
Biochemistry
title_short The two isoforms of Lyn display different intramolecular fuzzy complexes with the SH3 domain
title_full The two isoforms of Lyn display different intramolecular fuzzy complexes with the SH3 domain
title_fullStr The two isoforms of Lyn display different intramolecular fuzzy complexes with the SH3 domain
title_full_unstemmed The two isoforms of Lyn display different intramolecular fuzzy complexes with the SH3 domain
title_sort The two isoforms of Lyn display different intramolecular fuzzy complexes with the SH3 domain
dc.creator.none.fl_str_mv Teixeira, Joao M. C.
Fuentes, Héctor
Bielskutė, Stasė
Gairí Tahull, Margarida
Zerko, Szymon
Kozminski, Wiktor
Pons Vallès, Miquel
author Teixeira, Joao M. C.
author_facet Teixeira, Joao M. C.
Fuentes, Héctor
Bielskutė, Stasė
Gairí Tahull, Margarida
Zerko, Szymon
Kozminski, Wiktor
Pons Vallès, Miquel
author_role author
author2 Fuentes, Héctor
Bielskutė, Stasė
Gairí Tahull, Margarida
Zerko, Szymon
Kozminski, Wiktor
Pons Vallès, Miquel
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Proteïnes quinases
Ressonància magnètica nuclear
Bioquímica
Protein kinases
Nuclear magnetic resonance
Biochemistry
topic Proteïnes quinases
Ressonància magnètica nuclear
Bioquímica
Protein kinases
Nuclear magnetic resonance
Biochemistry
description The function of the intrinsically disordered Unique domain of the Src family of tyrosine kinases (SFK), where the largest differences between family members are concentrated, remains poorly understood. Recent studies in c-Src have demonstrated that the Unique region forms transient interactions, described as an intramolecular fuzzy complex, with the SH3 domain and suggested that similar complexes could be formed by other SFKs. Src and Lyn are members of a distinct subfamily of SFKs. Lyn is a key player in the immunologic response and exists in two isoforms originating from alternative splicing in the Unique domain. We have used NMR to compare the intramolecular interactions in the two isoforms and found that the alternatively spliced segment interacts specifically with the so-called RT-loop in the SH3 domain and that this interaction is abolished when a polyproline ligand binds to the SH3 domain. These results support the generality of the fuzzy complex formation in distinct subfamilies of SFKs and its physiological role, as the naturally occurring alternative splicing modulates the interactions in this complex.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/125625
url https://hdl.handle.net/2445/125625
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/molecules23112731
Molecules, 2018, vol. 23, num. 11, p. 2731
https://doi.org/10.3390/molecules23112731
dc.rights.none.fl_str_mv cc-by (c) Teixeira, Joao M. C. et al., 2018
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Teixeira, Joao M. C. et al., 2018
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Química Inorgànica i Orgànica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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