biostudies-literatureJohnston CANEI NIH HHSNIGMS NIH HHS11390-400https://www.ebi.ac.uk/biostudies/studies/S-EPMC2597383biostudies-literatureUnknown45(38)G-proteins cycle between an inactive GDP-bound state and an active GTP-bound state, serving as molecular switches that coordinate cellular signaling. We recently used phage display to identify a series of peptides that bind G alpha subunits in a nucleotide-dependent manner [Johnston, C. A., Willard, F. S., Jezyk, M. R., Fredericks, Z., Bodor, E. T., Jones, M. B., Blaesius, R., Watts, V. J., Harden, T. K., Sondek, J., Ramer, J. K., and Siderovski, D. P. (2005) Structure 13, 1069-1080]. Here we describe the structural features and functions of KB-1753, a peptide that binds selectively to GDP x AlF4(-)- and GTPgammaS-bound states of G alpha(i) subunits. KB-1753 blocks interaction of G alpha(transducin) with its effector, cGMP phosphodiesterase, and inhibits transducin-mediated activation of cBiochemistryMinimal determinants for binding activated G alpha from the structure of a G alpha(i1)-peptide dimer.PMC2597383EY128591 F32 GM076944R01 EY012859-06F32 GM076944-02R01 GM074268R01 GM074268-03F32 GM076944-01F32 GM076944R01 GM074268-01A1R01 EY012859R01 GM074268-02Lobanova ESBlaesius RRamer JKKuhlman BArshavsky VYFredericks ZJohnston CALow JWillard FSSiderovski DPShavkunov ASfalseMinimal determinants for binding activated G alpha from the structure of a G alpha(i1)-peptide dimer.G-proteins cycle between an inactive GDP-bound state and an active GTP-bound state, serving as molecular switches that coordinate cellular signaling. We recently used phage display to identify a series of peptides that bind G alpha subunits in a nucleotide-dependent manner [Johnston, C. A., Willard, F. S., Jezyk, M. R., Fredericks, Z., Bodor, E. T., Jones, M. B., Blaesius, R., Watts, V. J., Harden, T. K., Sondek, J., Ramer, J. K., and Siderovski, D. P. (2005) Structure 13, 1069-1080]. Here we describe the structural features and functions of KB-1753, a peptide that binds selectively to GDP x AlF4(-)- and GTPgammaS-bound states of G alpha(i) subunits. KB-1753 blocks interaction of G alpha(transducin) with its effector, cGMP phosphodiesterase, and inhibits transducin-mediated activation of c2006-01-01T00:00:00Z2006 Sep2025-04-05T15:40:41.951Z2019-03-27T00:19:42ZS-EPMC25973831698169910.1021/bi0613832