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A Myristoyl Binding Site in the SH3 Domain Modulates c-Src Membrane Anchoring

24 Pages Posted: 29 Jan 2019 Sneak Peek Status: Published

See all articles by Anabel Lise Le Roux

Anabel Lise Le Roux

University of Barcelona - BioNMR Laboratory

Irrem-Laareb Mohammad

University of Barcelona - BioNMR Laboratory

Borja Mateos

University of Barcelona - BioNMR Laboratory

Miguel Arbesú

University of Barcelona - BioNMR Laboratory

Farman Ali Khan

University of Barcelona - BioNMR Laboratory

João M. C. Teixeira

University of Barcelona - BioNMR Laboratory

Miquel Pons

University of Barcelona - BioNMR Laboratory

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Abstract

The c-Src oncogene is anchored to the cytoplasmic membrane through its N-terminal myristoylated SH4 domain. This domain is part of an intramolecular fuzzy complex with the SH3 and Unique domains. Here we show that the N-terminal myristoyl group binds to the SH3 domain in the proximity of the RT loop, when Src is not anchored to a lipid membrane. Residues in the so-called Unique Lipid Binding Region modulate this interaction. In the presence of lipids, the myristoyl group is released from the SH3 domain and inserts into the lipid membrane. The fuzzy complex with the SH4 and Unique domains is retained in the membrane bound form, placing the SH3 domain close to the membrane surface and restricting its orientation. The apparent affinity of myristoylated proteins containing the SH4, Unique and SH3 domains is modulated by these intramolecular interactions, suggesting a mechanism linking c-Src activation and membrane anchoring.

Suggested Citation

Le Roux, Anabel Lise and Mohammad, Irrem-Laareb and Mateos, Borja and Arbesú, Miguel and Khan, Farman Ali and Teixeira, João M. C. and Pons, Miquel, A Myristoyl Binding Site in the SH3 Domain Modulates c-Src Membrane Anchoring (2018). Available at SSRN: https://ssrn.com/abstract=3238694 or http://dx.doi.org/10.2139/ssrn.3238694
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Anabel Lise Le Roux

University of Barcelona - BioNMR Laboratory

Gran Via de les Corts Catalanes, 585
Barcelona, LA 08007
Spain

Irrem-Laareb Mohammad

University of Barcelona - BioNMR Laboratory

Gran Via de les Corts Catalanes, 585
Barcelona, LA 08007
Spain

Borja Mateos

University of Barcelona - BioNMR Laboratory

Gran Via de les Corts Catalanes, 585
Barcelona, LA 08007
Spain

Miguel Arbesú

University of Barcelona - BioNMR Laboratory

Gran Via de les Corts Catalanes, 585
Barcelona, LA 08007
Spain

Farman Ali Khan

University of Barcelona - BioNMR Laboratory

Gran Via de les Corts Catalanes, 585
Barcelona, LA 08007
Spain

João M. C. Teixeira

University of Barcelona - BioNMR Laboratory

Gran Via de les Corts Catalanes, 585
Barcelona, LA 08007
Spain

Miquel Pons (Contact Author)

University of Barcelona - BioNMR Laboratory ( email )

Gran Via de les Corts Catalanes, 585
Barcelona, LA 08007
Spain

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