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.
- MeSH
- cirkulární dichroismus MeSH
- fosforylace MeSH
- hmotnostní spektrometrie MeSH
- lidé MeSH
- maloúhlový rozptyl MeSH
- proteiny 14-3-3 chemie genetika metabolismus MeSH
- proteiny aktivující GTPasu chemie genetika metabolismus MeSH
- proteiny vázající GTP chemie genetika metabolismus MeSH
- rezonanční přenos fluorescenční energie MeSH
- sekundární struktura proteinů MeSH
- signální transdukce MeSH
- terciární struktura proteinů MeSH
- vazba proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
