GoLocoLGN motif, putative GEFs specific for G-alpha GTPases
|SMART accession number:||SM00390|
|Description:||GEF specific for Galpha_i proteins|
|Interpro abstract (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 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. 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:
|GO process:||signal transduction (GO:0007165)|
|GO function:||GTPase regulator activity (GO:0030695)|
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