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Structure. 2015 May 5;23(5):893-902. doi: 10.1016/j.str.2015.03.009. Epub 2015 Apr 23.

The SH3 Domain Acts as a Scaffold for the N-Terminal Intrinsically Disordered Regions of c-Src.

Author information

1
BioNMR Laboratory, Organic Chemistry Department, University of Barcelona, Baldiri Reixac 10-12, 08028 Barcelona, Spain.
2
BioNMR Laboratory, Organic Chemistry Department, University of Barcelona, Baldiri Reixac 10-12, 08028 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10-12, 08028 Barcelona, Spain.
3
CNRS UMR5237, University of Montpellier, CRBM, 1919 route de Mende, 34000 Montpellier, France.
4
BioNMR Laboratory, Organic Chemistry Department, University of Barcelona, Baldiri Reixac 10-12, 08028 Barcelona, Spain. Electronic address: mpons@ub.edu.

Abstract

Regulation of c-Src activity by the intrinsically disordered Unique domain has recently been demonstrated. However, its connection with the classical regulatory mechanisms is still missing. Here we show that the Unique domain is part of a long loop closed by the interaction of the SH4 and SH3 domains. The conformational freedom of the Unique domain is further restricted through direct contacts with SH3 that are allosterically modulated by binding of a poly-proline ligand in the presence and in the absence of lipids. Our results highlight the scaffolding role of the SH3 domain for the c-Src N-terminal intrinsically disordered regions and suggest a connection between the regulatory mechanisms involving the SH3 and Unique domains.

PMID:
25914053
DOI:
10.1016/j.str.2015.03.009
[Indexed for MEDLINE]
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