GoLoco motif is a protein

structural motif In a polymer, chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a common Biomolecular structure#Tertiary structure, three-dimensional structure that appears in a variety of different, evolutionarily unrel ...

. In

heterotrimeric G-protein Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a heterotrimeric complex. The biggest non-structura ...

signalling, cell surface receptors (

GPCRs G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

) are coupled to membrane-associated heterotrimers comprising a GTP-hydrolyzing subunit

G-alpha G alpha subunits are one of the three types of subunit of guanine nucleotide binding proteins, which are membrane-associated, heterotrimeric G proteins. Background G proteins and their receptors ( GPCRs) form one of the most prevalent signalling ...

and a

G-beta/G-gamma The G beta-gamma complex (Gβγ) is a tightly bound dimeric protein complex, composed of one Gβ and one Gγ subunit, and is a component of heterotrimeric G proteins. Heterotrimeric G proteins, also called guanosine nucleotide-binding proteins, c ...

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 (se
PDOC50132
, and guanine dissociation inhibitors (GDIs), which inhibit GDP dissociation. The GoLoco or G-protein regulatory (GPR) motif found in various G-protein regulators. acts as a GDI on G-alpha(i).

Structure

The crystal structure of the GoLoco motif in complex with G-alpha(i) has been solved. 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 In molecular biology, an arginine finger is an amino acid residue of some enzymes. Arginine fingers are often found in the protein superfamily of AAA+ ATPases, GTPases, and dUTPases, where they assist in the catalysis of the gamma phosphate or gamm ...

employed in GTPase-activating protein (se
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.

Examples

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: *

GPSM1 G-protein-signaling modulator 1 is a protein that in humans is encoded by the ''GPSM1'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generati ...

, GPSM2, GPSM3 *

PCP2 PCP site 2 is a binding site that was identified as a high-affinity target for phencyclidine (PCP), an anesthetic and dissociative hallucinogen that acts primarily as an NMDA receptor antagonist. The site is distinct from the PCP binding site ...

* RAP1GAP. RGS12, RGS14

References

Membrane proteins {{membrane-protein-stub