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Topology and Grb2 interactions of the intrinsically disordered platform protein Gab1

Subject Area Biochemistry
Biophysics
Term from 2017 to 2021
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 374605181
 
By and large it remains an enigma how the numerous signals received by cells through their many surface receptors are effectively processed on the molecular level towards one specific cellular response. Shedding more light onto these higher order processes of molecular signal computation is a burning issue in modern signal transduction research and in cell biology in general. In the proposed project, intrinsically disordered proteins of the Gab family will be studied, which are highly dynamic assembly platforms for large multi-protein complexes computing intracellular signals. We combine cell biology, biochemical and structural biology studies to characterize the assembly of Grb2 and Gab1 and, subsequently, the docking of other associating signaling proteins (like PI3 kinase) on phosphorylated Gab1. From these molecular insights into the supramolecular organization of Gab1 and its variation by post-translational modifications, we expect to unravel fundamental principles of molecular signal computation, as well as improving our understanding of the physiological and pathological roles of the ubiquitous Gab proteins.
DFG Programme Research Grants
 
 

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