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The Two Isoforms of Lyn Display Different Intramolecular Fuzzy Complexes with the SH3 Domain

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dc.abstract.enThe 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.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorFuentes, Héctor
dc.contributor.authorTeixeira, João M. C.
dc.contributor.authorGairi, Margarida
dc.contributor.authorBielskut, Stase˙
dc.contributor.authorPons, Miquel
dc.contributor.authorŻerko, Szymon
dc.contributor.authorKoźmiński, Wiktor
dc.date.accessioned2024-01-26T10:49:53Z
dc.date.available2024-01-26T10:49:53Z
dc.date.copyright2018-10-23
dc.date.issued2018
dc.description.accesstimeAT_PUBLICATION
dc.description.financeNie dotyczy
dc.description.number11
dc.description.versionFINAL_PUBLISHED
dc.description.volume23
dc.identifier.doi10.3390/MOLECULES23112731
dc.identifier.issn1420-3049
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/123252
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofMolecules
dc.relation.pagesart.no. 2731
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.enSrc family kinases
dc.subject.enSrc
dc.subject.enLyn
dc.subject.enSH3 domains
dc.subject.enintrinsically disordered proteins
dc.subject.enfuzzy complexes
dc.subject.enSFKs unique domains
dc.subject.ennuclear magnetic resonance
dc.subject.enFarseer-NMR
dc.titleThe Two Isoforms of Lyn Display Different Intramolecular Fuzzy Complexes with the SH3 Domain
dc.typeJournalArticle
dspace.entity.typePublication