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...
| Authors: | ; ; ; ; ; ; |
|---|---|
| Format: | Article |
| Status: | Published version |
| Publication date: | 2018 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/125625 |
| Online Access: | https://hdl.handle.net/2445/125625 |
| Access Level: | Open access |
| Keyword: | Proteïnes quinases Ressonància magnètica nuclear Bioquímica Protein kinases Nuclear magnetic resonance Biochemistry |
| _version_ | 1878735349244493824 |
|---|---|
| author | Teixeira, Joao M. C. |
| author2 | Fuentes, Héctor Bielskutė, Stasė Gairí Tahull, Margarida Zerko, Szymon Kozminski, Wiktor Pons Vallès, Miquel |
| author2_role | author author author author author author |
| author_browse | Bielskutė, Stasė Fuentes, Héctor Gairí Tahull, Margarida Kozminski, Wiktor Pons Vallès, Miquel Teixeira, Joao M. C. Zerko, Szymon |
| author_facet | Teixeira, Joao M. C. Fuentes, Héctor Bielskutė, Stasė Gairí Tahull, Margarida Zerko, Szymon Kozminski, Wiktor Pons Vallès, Miquel |
| author_role | author |
| collection | Dipòsit Digital de la UB |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_7af3edde4ce57b1b2ff5d3cd2bc8decc |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/125625 |
| publishDate | 2018 |
| publishDateSort | 2018 |
| publisher | MDPI |
| publisherStr | MDPI |
| reponame_str | Dipòsit Digital de la UB |
| spelling | The two isoforms of Lyn display different intramolecular fuzzy complexes with the SH3 domain Teixeira, Joao M. C. Fuentes, Héctor Bielskutė, Stasė Gairí Tahull, Margarida Zerko, Szymon Kozminski, Wiktor Pons Vallès, Miquel Proteïnes quinases Ressonància magnètica nuclear Bioquímica Protein kinases Nuclear magnetic resonance Biochemistry 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. MDPI https://hdl.handle.net/2445/125625 |
| 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 |
| status_str | publishedVersion |
| title | 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_short | 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 |
| topic | Proteïnes quinases Ressonància magnètica nuclear Bioquímica Protein kinases Nuclear magnetic resonance Biochemistry |
| topic_facet | Proteïnes quinases Ressonància magnètica nuclear Bioquímica Protein kinases Nuclear magnetic resonance Biochemistry |
| url | https://hdl.handle.net/2445/125625 |