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Molecules 2018, 23(11), 2731; https://doi.org/10.3390/molecules23112731

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

1
BioNMR Laboratory, Inorganic and Organic Chemistry Department, University of Barcelona; Baldiri Reixac, 08028 Barcelona, Spain
2
Institute of Chemical Physics, Vilnius University, Saulétekio al.3, 10257 Vilnius, Lithuania
3
LRB, Scientific and Technologic Centers of the University of Barcelona, Baldiri Reixac, 08028 Barcelona, Spain
4
Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw; Żwirki i Wigury 101, 02-089 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Received: 10 October 2018 / Revised: 19 October 2018 / Accepted: 21 October 2018 / Published: 23 October 2018
(This article belongs to the Section Chemical Biology)
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Abstract

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. View Full-Text
Keywords: Src family kinases; Src; Lyn; SH3 domains; intrinsically disordered proteins; fuzzy complexes; SFKs unique domains; nuclear magnetic resonance; Farseer-NMR Src family kinases; Src; Lyn; SH3 domains; intrinsically disordered proteins; fuzzy complexes; SFKs unique domains; nuclear magnetic resonance; Farseer-NMR
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Teixeira, J.M.C.; Fuentes, H.; Bielskutė, S.; Gairi, M.; Żerko, S.; Koźmiński, W.; Pons, M. The Two Isoforms of Lyn Display Different Intramolecular Fuzzy Complexes with the SH3 Domain. Molecules 2018, 23, 2731.

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