Structural basis for the 14-3-3 protein-dependent inhibition of the regulator of G protein signaling 3 (RGS3) function |
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Authors: | Rezabkova Lenka Man Petr Novak Petr Herman Petr Vecer Jaroslav Obsilova Veronika Obsil Tomas |
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Institution: | Department of Physical and Macromolecular Chemistry, Charles University in Prague, 12843 Prague, Czech Republic. |
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Abstract: | Regulator of G protein signaling (RGS) proteins function as GTPase-activating proteins for the α-subunit of heterotrimeric G proteins. The function of certain RGS proteins is negatively regulated by 14-3-3 proteins, a family of highly conserved regulatory molecules expressed in all eukaryotes. In this study, we provide a structural mechanism for 14-3-3-dependent inhibition of RGS3-Gα interaction. We have used small angle x-ray scattering, hydrogen/deuterium exchange kinetics, and Förster resonance energy transfer measurements to determine the low-resolution solution structure of the 14-3-3ζ·RGS3 complex. The structure shows the RGS domain of RGS3 bound to the 14-3-3ζ dimer in an as-yet-unrecognized manner interacting with less conserved regions on the outer surface of the 14-3-3 dimer outside its central channel. Our results suggest that the 14-3-3 protein binding affects the structure of the Gα interaction portion of RGS3 as well as sterically blocks the interaction between the RGS domain and the Gα subunit of heterotrimeric G proteins. |
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Keywords: | Fluorescence Resonance Energy Transfer (FRET) Phosphorylation RGS Proteins Signal Transduction Structural Biology 14-3-3 Protein H/D Exchange SAXS Low-resolution Structure |
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