GGLG protein gamma subunit-like motifs
|SMART accession number:||SM00224|
|Interpro abstract (IPR015898):|
This entry represents the G protein gamma subunit and the GGL (G protein gamma-like) domain, which are related in sequence and are comprised of an extended alpha-helical polypeptide. The G protein gamma subunit forms a stable dimer with the beta subunit, but it does not make any contact with the alpha subunit, which contacts the opposite face of the beta subunit. The GGL domain is found in several RGS (regulators of G protein signaling) proteins. GGL domains can interact with beta subunits to form novel dimers that prevent gamma subunit binding, and may prevent heterotrimer formation by inhibiting alpha subunit binding. The interaction between G protein beta-5 neuro-specific isoforms and RGS GGL domains may represent a general mode of binding between beta-propeller proteins and their partners [(PUBMED:11331068)].
|GO process:||G-protein coupled receptor signaling pathway (GO:0007186)|
|GO component:||heterotrimeric G-protein complex (GO:0005834)|
|GO function:||signal transducer activity (GO:0004871)|
Click on the following links for more information.
- Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing GGL domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with GGL domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing GGL domain in the selected taxonomic class.
- Cellular role (predicted cellular role)
Cellular role: signalling
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Snow BE et al.
- A G protein gamma subunit-like domain shared between RGS11 and other RGS proteins specifies binding to Gbeta5 subunits.
- Proc Natl Acad Sci U S A. 1998; 95: 13307-12
- Display abstract
Regulators of G protein signaling (RGS) proteins act as GTPase-activating proteins (GAPs) toward the alpha subunits of heterotrimeric, signal-transducing G proteins. RGS11 contains a G protein gamma subunit-like (GGL) domain between its Dishevelled/Egl-10/Pleckstrin and RGS domains. GGL domains are also found in RGS6, RGS7, RGS9, and the Caenorhabditis elegans protein EGL-10. Coexpression of RGS11 with different Gbeta subunits reveals specific interaction between RGS11 and Gbeta5. The expression of mRNA for RGS11 and Gbeta5 in human tissues overlaps. The Gbeta5/RGS11 heterodimer acts as a GAP on Galphao, apparently selectively. RGS proteins that contain GGL domains appear to act as GAPs for Galpha proteins and form complexes with specific Gbeta subunits, adding to the combinatorial complexity of G protein-mediated signaling pathways.
- Garcia-Higuera I et al.
- Folding of proteins with WD-repeats: comparison of six members of the WD-repeat superfamily to the G protein beta subunit.
- Biochemistry. 1996; 35: 13985-94
- Display abstract
The family of WD-repeat proteins comprises over 30 different proteins that share a highly conserved repeating motif [Neer, E. J., Schmidt, C. J., Nambudripad, R., & Smith, T. F. (1994) Nature 371, 297-300]. Members of this family include the signal-transducing G protein beta subunit, as well as other proteins that regulate signal transduction, transcription, pre-mRNA splicing, cytoskeletal organization, and vesicular fusion. The crystal structure of one WD-repeat protein (G beta) has now been solved (Wall et al., 1995; Sondek et al, 1996) and reveals that the seven repeating units form a circular, propeller-like structure with seven blades each made up of four beta strands. It is very likely that all WD-repeat proteins form a similar structure. If so, it will be possible to use information about important surface regions of one family member to predict properties of another. If WD proteins form structures similar to G beta, their hydrodynamic properties should be those of compact, globular proteins, and they should be resistant to cleavage by trypsin. However, the only studied example of a WD-repeat protein, G beta, synthesized in vitro in a rabbit reticulocyte lysate, is unable to fold into a native structure without its partner protein G gamma. The non-WD-repeat amino terminal alpha helix of G beta does not inhibit folding because G beta does not fold even when this region is removed. It is not known whether all WD-repeat proteins are unable to fold when synthesized in an in vitro system. We synthesized seven members of the family in a rabbit reticulocyte lysate, determined their Stokes radius, sedimentation coefficient, and frictional ratio, and assayed their stability to trypsin. Our working definition of folding was that the proteins from globular, trypsin-resistant structures because, except for G beta gamma, their functions are not known or cannot be assayed in reticulocyte lysates. We chose proteins that include amino and carboxyl extensions as well as proteins that are made up entirely of WD-repeats. We show that unlike G beta, several proteins with WD-repeats are able to fold into globular proteins in a rabbit reticulocyte lysate. One protein, beta Trcp, formed large aggregates like G beta, suggesting that it may also require a partner protein. Despite the presence of many potential tryptic cleavage sites, all of the proteins that did fold gave stable large products on tryptic proteolysis, as predicted on the basis of the structure of G beta. These studies suggest that other WD-repeat proteins are likely to form propeller structures similar to G beta.
- Sondek J, Bohm A, Lambright DG, Hamm HE, Sigler PB
- Crystal structure of a G-protein beta gamma dimer at 2.1A resolution.
- Nature. 1996; 379: 369-74
- Display abstract
Many signalling cascades use seven-helical transmembrane receptors coupled to heterotrimeric G proteins (G alpha beta gamma) to convert extracellular signals into intracellular responses. Upon nucleotide exchange catalysed by activated receptors, heterotrimers dissociate into GTP-bound G alpha subunits and G beta gamma dimers, either of which can modulate many downstream effectors. Here we use multiwavelength anomalous diffraction data to solve the crystal structure of the beta gamma dimer of the G protein transducin. The beta-subunit is primarily a seven-bladed beta-propeller that is partially encircled by an extended gamma-subunit. The beta-propeller, which contains seven structurally similar WD repeats, defines the stereochemistry of the WD repeat and the probable architecture of all WD-repeat-containing domains. The structure details interactions between G protein beta- and gamma-subunits and highlights regions implicated in effector modulation for the conserved family of G protein beta gamma dimers.
- Hurley JB, Fong HK, Teplow DB, Dreyer WJ, Simon MI
- Isolation and characterization of a cDNA clone for the gamma subunit of bovine retinal transducin.
- Proc Natl Acad Sci U S A. 1984; 81: 6948-52
- Display abstract
We have isolated and characterized a cDNA clone that encodes the gamma subunit of transducin, the guanine nucleotide binding regulatory protein found in vertebrate photoreceptors. The gamma subunit was separated from the alpha and beta subunits of transducin and purified to homogeneity by reversed-phase high performance liquid chromatography. The sequence of the first 45 amino acids at the amino terminus of this polypeptide was then determined by automated Edman degradation. Oligodeoxynucleotide probes corresponding to two nonoverlapping regions of this sequence were synthesized and then used to screen a bovine retinal cDNA library. One probe, T gamma 1, was a mixture of 32 different heptadecamers complementary to all possible mRNA sequences that could encode a portion of the T gamma sequence; the other probe, T gamma 2, was a mixture of 128 different heptadecamers. Thirteen clones that hybridized with T gamma 1 were selected. Only one of these had an insert that also hybridized with T gamma 2. The DNA sequence of this insert encodes a 73-amino acid polypeptide that corresponds to the transducin gamma subunit on the basis of amino-terminal sequence, amino acid composition, and carboxyl-terminal sequence. The molecular weight of the mature gamma subunit is 8400. It appears to be synthesized as a discrete polypeptide and not as a domain of a larger precursor polyprotein. The transducin gamma subunit is very hydrophilic and acidic; it has 19 acidic and 11 basic amino acids as well as three cysteine residues. Furthermore, significant homology was found in comparisons of the nucleic acid sequence corresponding to the carboxyl terminus of the gamma transducin transcript with the sequences corresponding to the carboxyl terminus of ras oncogene products, suggesting a possible ancestral relationship between these genes.
- Metabolism (metabolic pathways involving proteins which contain this domain)
% proteins involved KEGG pathway ID Description 33.33 map04810 Regulation of actin cytoskeleton 33.33 map04742 Taste transduction 33.33 map04010 MAPK signaling pathway
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with GGL domain which could be assigned to a KEGG orthologous group, and not all proteins containing GGL domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of GGL domains in PDB
PDB code Main view Title 1a0r HETEROTRIMERIC COMPLEX OF PHOSDUCIN/TRANSDUCIN BETA-GAMMA 1b9x STRUCTURAL ANALYSIS OF PHOSDUCIN AND ITS PHOSPHORYLATION-REGULATED INTERACTION WITH TRANSDUCIN 1b9y STRUCTURAL ANALYSIS OF PHOSDUCIN AND ITS PHOSPHORYLATION-REGULATED INTERACTION WITH TRANSDUCIN BETA-GAMMA 1gg2 G PROTEIN HETEROTRIMER MUTANT GI_ALPHA_1(G203A) BETA_1 GAMMA_2 WITH GDP BOUND 1got HETEROTRIMERIC COMPLEX OF A GT-ALPHA/GI-ALPHA CHIMERA AND THE GT-BETA-GAMMA SUBUNITS 1gp2 G PROTEIN HETEROTRIMER GI_ALPHA_1 BETA_1 GAMMA_2 WITH GDP BOUND 1omw Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and gamma 2 subunits 1tbg BETA-GAMMA DIMER OF THE HETEROTRIMERIC G-PROTEIN TRANSDUCIN 1xhm The Crystal Structure of a Biologically Active Peptide (SIGK) Bound to a G Protein Beta:Gamma Heterodimer 2bcj Crystal Structure of G Protein-Coupled Receptor Kinase 2 in Complex with Galpha-q and Gbetagamma Subunits 2pbi The multifunctional nature of Gbeta5/RGS9 revealed from its crystal structure 2trc PHOSDUCIN/TRANSDUCIN BETA-GAMMA COMPLEX 3ah8 Structure of heterotrimeric G protein Galpha-q beta gamma in complex with an inhibitor YM-254890 3cik Human GRK2 in Complex with Gbetagamma subunits 3krw Human GRK2 in complex with Gbetgamma subunits and balanol (soak) 3krx Human GRK2 in complex with Gbetgamma subunits and balanol (co-crystal) 3psc Bovine GRK2 in complex with Gbetagamma subunits 3pvu Bovine GRK2 in complex with Gbetagamma subunits and a selective kinase inhibitor (CMPD101) 3pvw Bovine GRK2 in complex with Gbetagamma subunits and a selective kinase inhibitor (CMPD103A) 3sn6 Crystal structure of the beta2 adrenergic receptor-Gs protein complex 3uzs Structure of the C13.28 RNA Aptamer Bound to the G Protein-Coupled Receptor Kinase 2-Heterotrimeric G Protein Beta 1 and Gamma 2 Subunit Complex 3v5w Human G Protein-Coupled Receptor Kinase 2 in Complex with Soluble Gbetagamma Subunits and Paroxetine 4kfm Crystal structure of the G protein-gated inward rectifier K+ channel GIRK2 (Kir3.2) in complex with the beta-gamma G protein subunits 4mk0 Crystal structure of G protein-coupled receptor kinase 2 in complex with a a rationally designed paroxetine derivative
- Links (links to other resources describing this domain)
PFAM G_protein_gamma INTERPRO IPR015898 PROSITE G_PROTEIN_GAMMA