Crystal structure of RGS3 RGS domain
Evžen Bouřa1,2, Tomáš Obšil1,2
Department of Physical and Macromolecular Chemistry, Faculty of Science,
Charles University; 12843 Prague, Czech Republic
2 Institute of Physiology, Academy of Sciences of the Czech Republic; 14220 Prague, Czech Republic
RGS3 protein is a member of Regulator of G protein Signaling (RGS) family. RGS proteins are primarily known as negative regulators of G protein signalling pathways due to their function as GTPase activating proteins (GAPs) for the α subunit of heterotrimeric G proteins. The modulation of RGS action remains unclear but includes post-translational modifications, subcellular localization, and interactions with protein binding partners e.g. 14-3-3 protein.
The crystal structure of RGS3 RGS domain was determined at 2.3 Å resolution. It crystalized as a dimer connected by S-S bridge. The existence of the dimer was also proven in solution. The RGS domain is composed of nine α-helices that fold into two small subdomains. The terminal subdomain contains the N and C termini of the box and is formed by α1, α2, α3, α8, and α9. Helices α1 and α9 lie in antiparallel orientation, juxtaposing the N and C termini of the box. The larger bundle subdomain, formed by α4, α5, α6, and α7, is a classic right-handed, antiparallel four-helix bundle. Helices α7, α8, and α9 form essentially one continuous helix with two bends. The RGS domain comprises of aproximately 130 AA. Thirty of these AA are conserved within the RGS family. The RGS domain 3D structure is absolutely conserved within the RGS family. Our structural study supplies another prove of this fact.
This work was funded by Grant 204/06/0565 of the Grant Agency of the Czech Republic, by Grant KJB500110601 of the Grant Agency of the Academy of Sciences of the Czech Republic, by Research Project MSM0021620835 and Centre of Neurosciences LC554 of the Ministry of Education, Youth, and Sports of the Czech Republic, and by Research Project AV0Z50110509 of the Academy of Sciences of the Czech Republic.