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GoLoco motif information


GoLoco motif
crystal structure of human g[alpha]i1 bound to the goloco motif of rgs14
Identifiers
SymbolGoLoco
PfamPF02188
InterProIPR003109
SMARTGoLoco
SCOP21kjy / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

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]

  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. doi:10.1016/s0968-0004(99)01441-3. 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. Bibcode:2000PNAS...9714364D. 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. Bibcode:2002Natur.416..878K. doi:10.1038/416878a. PMID 11976690. S2CID 4406208.
  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. S2CID 22667367.
  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.

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