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10  structures 91  species 0  interactions 1105  sequences 99  architectures

Family: GoLoco (PF02188)

Summary: GoLoco motif

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GoLoco motif Edit Wikipedia article

GoLoco motif
PDB 1kjy EBI.jpg
crystal structure of human g[alpha]i1 bound to the goloco motif of rgs14
Identifiers
Symbol GoLoco
Pfam PF02188
InterPro IPR003109
SMART GoLoco
SCOP 1kjy
SUPERFAMILY 1kjy

GoLoco motif is a protein structural motif.[1][2][3]

In heterotrimeric G-protein signalling, cell surface receptors (GPCRs) are coupled to membrane-associated heterotrimers comprising a GTP-hydrolyzing subunit G-alpha and a G-beta/G-gamma dimer. The inactive form contains the alpha subunit bound to GDP and complexes with the beta and gamma subunit. When the ligand is associated to the receptor, GDP is displaced from G-alpha and GTP is bound. The GTP/G-alpha complex dissociates from the trimer and associates to an effector until the intrinsic GTPase activity of G-alpha returns the protein to GDP bound form. Reassociation of GDP-bound G-alpha with G-beta/G-gamma dimer terminates the signal. Several mechanisms regulate the signal output at different stage of the G-protein cascade. Two classes of intracellular proteins act as inhibitors of G protein activation: GTPase activating proteins (GAPs), which enhance GTP hydrolysis (see PDOC50132), and guanine dissociation inhibitors (GDIs), which inhibit GDP dissociation. The GoLoco or G-protein regulatory (GPR) motif found in various G-protein regulators.[1][4] acts as a GDI on G-alpha(i).[2][5]

Structure[edit]

The crystal structure of the GoLoco motif in complex with G-alpha(i) has been solved.[6] It consists of three small alpha helices. The highly conserved Asp-Gln-Arg triad within the GoLoco motif participates directly in GDP binding by extending the arginine side chain into the nucleotide binding pocket, highly reminiscent of the catalytic arginine finger employed in GTPase-activating protein (see PDOC50238). This addition of an arginine in the binding pocket affects the interaction of GDP with G-alpha and therefore is certainly important for the GoLoco GDI activity.[6]

Examples[edit]

Some proteins known to contain a GoLoco motif are listed below:

  • Mammalian regulators of G-protein signaling 12 and 14 (RGS12 and RGS14), multifaceted signal transduction regulators.
  • Loco, the drosophila RGS12 homologue.
  • Mammalian Purkinje-cell protein-2 (Pcp2). It may function as a cell-type specific modulator for G protein-mediated cell signaling. It is uniquely expressed in cerebellar Purkinje cells and in retinal bipolar neurons.
  • Eukaryotic Rap1GAP. A GTPase activator for the nuclear ras-related regulatory protein RAP-1A.
  • Drosophila protein Rapsynoid (also known as Partner of Inscuteable, Pins) and its mammalian homologues, AGS3 and LGN. They form a G-protein regulator family that also contains TPR repeats.

Human proteins containing this domain include:

References[edit]

  1. ^ a b Siderovski DP, Diversé-Pierluissi M, De Vries L (September 1999). "The GoLoco motif: a Galphai/o binding motif and potential guanine-nucleotide exchange factor". Trends Biochem. Sci. 24 (9): 340–1. PMID 10470031. 
  2. ^ a b De Vries L, Fischer T, Tronchère H, Brothers GM, Strockbine B, Siderovski DP, Farquhar MG (December 2000). "Activator of G protein signaling 3 is a guanine dissociation inhibitor for Galpha i subunits". Proc. Natl. Acad. Sci. U.S.A. 97 (26): 14364–9. doi:10.1073/pnas.97.26.14364. PMC 18924. PMID 11121039. 
  3. ^ Kimple RJ, Kimple ME, Betts L, Sondek J, Siderovski DP (April 2002). "Structural determinants for GoLoco-induced inhibition of nucleotide release by Galpha subunits". Nature 416 (6883): 878–81. doi:10.1038/416878a. PMID 11976690. 
  4. ^ Ponting CP (1999). "Raf-like Ras/Rap-binding domains in RGS12- and still-life-like signalling proteins". J. Mol. Med. 77 (10): 695–698. doi:10.1007/s001099900054. PMID 10606204. 
  5. ^ Artemyev NO, Natochin M, Lester B, Peterson YK, Bernard ML, Lanier SM (2000). "AGS3 inhibits GDP dissociation from galpha subunits of the Gi family and rhodopsin-dependent activation of transducin". J. Biol. Chem. 275 (52): 40981–40985. doi:10.1074/jbc.M006478200. PMID 11024022. 
  6. ^ a b Siderovski DP, Kimple RJ, Kimple ME, Betts L, Sondek J (2002). "Structural determinants for GoLoco-induced inhibition of nucleotide release by Galpha subunits". Nature 416 (6883): 878–881. doi:10.1038/416878a. PMID 11976690. 

This article incorporates text from the public domain Pfam and InterPro IPR003109


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Literature references

  1. Siderovski DP, Diverse-Pierluissi M, De Vries L; , Trends Biochem Sci 1999;24:340-341.: The GoLoco motif: a Galphai/o binding motif and potential guanine-nucleotide exchange factor. PUBMED:10470031 EPMC:10470031

  2. De Vries L, Fischer T, Tronchere H, Brothers GM, Strockbine B, Siderovski DP, Farquhar MG; , Proc Natl Acad Sci U S A 2000;97:14364-14369.: Activator of G protein signaling 3 is a guanine dissociation inhibitor for Galpha i subunits. PUBMED:11121039 EPMC:11121039

  3. Kimple RJ, Kimple ME, Betts L, Sondek J, Siderovski DP; , Nature 2002;416:878-881.: Structural determinants for GoLoco-induced inhibition of nucleotide release by Galpha subunits. PUBMED:11976690 EPMC:11976690


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003109

In heterotrimeric G-protein signalling, cell surface receptors (GPCRs) are coupled to membrane-associated heterotrimers comprising a GTP-hydrolysing subunit G-alpha and a G-beta/G-gamma dimer. The inactive form contains the alpha subunit bound to GDP and complexes with the beta and gamma subunit. When the ligand is associated to the receptor, GDP is displaced from G-alpha and GTP is bound. GTP/G-alpha complex dissociates from the trimer and associates to an effector until the intrinsic GTPase activity of G-alpha returns the protein to GDP bound form. Reassociation of GDP bound G-alpha with G-beta/G-gamma dimer terminates the signal. Several mechanisms regulate the signal output at different stage of the G-protein cascade. Two classes of intracellular proteins act as inhibitors of G protein activation: GTPase activating proteins (GAPs), which enhance GTP hydrolysis (see PROSITEDOC), and guanine dissociation inhibitors (GDIs), which inhibit GDP dissociation. The GoLoco or G-protein regulatory (GPR) motif found in various G-protein regulators [PUBMED:10470031, PUBMED:10606204] acts as a GDI on G-alpha(i) [PUBMED:11121039, PUBMED:11024022].

The crystal structure of the GoLoco motif in complex with G-alpha(i) has been solved [PUBMED:11976690]. It consists of three small alpha helices. The highly conserved Asp-Gln-Arg triad within the GoLoco motif participates directly in GDP binding by extending the arginine side chain into the nucleotide binding pocket, highly reminiscent of the catalytic arginine finger employed in GTPase-activating protein (see PROSITEDOC). This addition of an arginine in the binding pocket affects the interaction of GDP with G-alpha and therefore is certainly important for the GoLoco GDI activity [PUBMED:11976690].

Some proteins known to contain a GoLoco motif are listed below:

  • Mammalian regulators of G-protein signalling 12 and 14 (RGS12 and RGS14), multifaceted signal transduction regulators.
  • Loco, the drosophila RGS12 homologue.
  • Mammalian Purkinje-cell protein-2 (Pcp2). It may function as a cell-type specific modulator for G protein-mediated cell signalling. It is uniquely expressed in cerebellar Purkinje cells and in retinal bipolar neurons.
  • Eukaryotic Rap1GAP. A GTPase activator for the nuclear ras-related regulatory protein RAP-1A.
  • Drosophila protein Rapsynoid (also known as Partner of Inscuteable, Pins) and its mammalian homologues AGS3 and LGN. They form a G-protein regulator family that also contains TPR repeats.

Gene Ontology

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Domain organisation

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Full
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Representative proteomes NCBI
(983)
Meta
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RP15
(104)
RP35
(151)
RP55
(308)
RP75
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  Seed
(46)
Full
(1105)
Representative proteomes NCBI
(983)
Meta
(0)
RP15
(104)
RP35
(151)
RP55
(308)
RP75
(542)
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Curation and family details

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Seed source: Alignment kindly provided by SMART
Previous IDs: none
Type: Motif
Author: SMART
Number in seed: 46
Number in full: 1105
Average length of the domain: 22.80 aa
Average identity of full alignment: 44 %
Average coverage of the sequence by the domain: 8.24 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.7 20.7
Trusted cut-off 21.0 21.2
Noise cut-off 20.5 20.6
Model length: 23
Family (HMM) version: 12
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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the GoLoco domain has been found. There are 10 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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