Related Experiment Video
Updated: Jun 17, 2026

A High-content Imaging Workflow to Study Grb2 Signaling Complexes by Expression Cloning
Published on: October 30, 2012
Assembly of the Sos1-Grb2-Gab1 ternary signaling complex is under allosteric control
Caleb B McDonald1, Kenneth L Seldeen, Brian J Deegan
1Department of Biochemistry & Molecular Biology and USylvester Braman Family Breast Cancer Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Abstract:
Allostery has evolved as a form of local communication between interacting protein partners allowing them to quickly sense changes in their immediate vicinity in response to external cues. Herein, using isothermal titration calorimetry (ITC) in conjunction with circular dichroism (CD) and macromolecular modeling (MM), we show that the binding of Grb2 adaptor--a key signaling molecule involved in the activation of Ras GTPase--to its downstream partners Sos1 guanine nucleotide exchange factor and Gab1 docker is under tight allosteric regulation. Specifically, our findings reveal that the binding of one molecule of Sos1 to the nSH3 domain allosterically induces a conformational change within Grb2 such that the loading of a second molecule of Sos1 onto the cSH3 domain is blocked and, in so doing, allows Gab1 access to the cSH3 domain in an exclusively non-competitive manner to generate the Sos1-Grb2-Gab1 ternary signaling complex.
More Related Videos
Related Concept Videos
Assembly of Signaling Complexes
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Amplifying Signals via Enzymatic Cascade
Activation and Inactivation of G Proteins
Coat Assembly and GTPases
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
TGF - β Signaling Pathway
Cooperative Allosteric Transitions

