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Updated: Apr 14, 2026

Combining X-Ray Crystallography with Small Angle X-Ray Scattering to Model Unstructured Regions of Nsa1 from S. Cerevisiae
Published on: January 10, 2018
The SH3 Domain Acts as a Scaffold for the N-Terminal Intrinsically Disordered Regions of c-Src
Mariano Maffei1, Miguel Arbesú1, Anabel-Lise Le Roux2
1BioNMR Laboratory, Organic Chemistry Department, University of Barcelona, Baldiri Reixac 10-12, 08028 Barcelona, Spain.
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.
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