RGS domain (IPR016137)
Short name: RGS
- RGS domain (IPR016137)
This entry represents a structural domain with a multi-helical fold consisting of a 4-helical bundle with a left-handed twist and an up-and-down topology. This domain can be divided into two all-alpha subdomains. This domain is found in regulation of G-protein signalling (RGS) proteins, as well as other related proteins, including:
- RGS4 [PMID: 9108480].
- RGS9 [PMID: 11234020].
- G-alpha interacting protein GaIP [PMID: 10452897].
- Axin [PMID: 10811618].
- p115RhoGEF [PMID: 11524686].
- Pdz-RhoGEF [PMID: 11470431].
- G-protein coupled receptor kinase 2 N-terminal domain [PMID: 12764189].
RGS (Regulator of G Protein Signalling) proteins are multi-functional, GTPase-accelerating proteins that promote GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways. Upon activation by GPCRs, heterotrimeric G proteins exchange GDP for GTP, are released from the receptor, and dissociate into free, active GTP-bound alpha subunit and beta-gamma dimer, both of which activate downstream effectors. The response is terminated upon GTP hydrolysis by the alpha subunit (IPR001019), which can then bind the beta-gamma dimer (IPR001632, IPR001770) and the receptor. RGS proteins markedly reduce the lifespan of GTP-bound alpha subunits by stabilising the G protein transition state.
All RGS proteins contain an 'RGS-box' (or RGS domain), which is required for activity. Some small RGS proteins such as RGS1 and RGS4 are comprised of little more than an RGS domain, while others also contain additional domains that confer further functionality. RGS domains can be found in conjunction with a variety of domains, including: DEP for membrane targeting (IPR000591), PDZ for binding to GPCRs (IPR001478), PTB for phosphotyrosine-binding (IPR006020), RBD for Ras-binding (IPR003116), GoLoco for guanine nucleotide inhibitor activity (IPR003109), PX for phosphatidylinositol-binding (IPR001683), PXA that is associated with PX (IPR003114), PH for stimulating guanine nucleotide exchange (IPR001849), and GGL (G protein gamma subunit-like) for binding G protein beta subunits (IPR001770). Those RGS proteins that contain GGL domains can interact with G protein beta subunits to form novel dimers that prevent G protein gamma subunit binding and G protein alpha subunit association, thereby preventing heterotrimer formation.