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Insights into the Conformational Plasticity of the Protein Kinase Akt1 by Multi-Lateral Dipolar Spectroscopy
Juliane Stehle1, Jörn Weisner2, Leanne Eichhorn1
1Department of Chemistry and, Konstanz Research School Chemical Biology (KoRS-CB), University of Konstanz, Universitätsstraße 10, 78457, Konstanz, Germany.
Abstract:
The serine/threonine kinase Akt1 is part of the PI3 K/Akt pathway and plays a key role in the regulation of various cellular processes such as cell growth, proliferation, and apoptosis. Here, we analyzed the elasticity between the two domains of the kinase Akt1, connected by a flexible linker, recording a wide variety of distance restraints by electron paramagnetic resonance (EPR) spectroscopy. We studied full length Akt1 and the influence of the cancer-associated mutation E17K. The conformational landscape in the presence of different modulators, like different types of inhibitors and membranes was presented, revealing a tuned flexibility between the two domains, dependent on the bound molecule.
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