2G83

Structure of activated G-alpha-i1 bound to a nucleotide-state-selective peptide: Minimal determinants for recognizing the active form of a G protein alpha subunit

2G83 の概要

• エントリーDOI: 10.2210/pdb2g83/pdb
• 分子名称: Guanine nucleotide-binding protein G(i), alpha-1 subunit, KB-1753 phage display peptide, TETRAFLUOROALUMINATE ION, ... (6 entities in total)
• 機能のキーワード: guanine-nucleotide binding protein, phage display peptide, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus (By similarity): P63096
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 75553.65

構造登録者

Johnston, C.A.,Ramer, J.K.,Blaesius, R.,Kuhlman, B.,Arshavsky, V.Y.,Siderovski, D.P. (登録日: 2006-03-01, 公開日: 2006-10-10, 最終更新日: 2024-12-25)

主引用文献

Johnston, C.A.,Lobanova, E.S.,Shavkunov, A.S.,Low, J.,Ramer, J.K.,Blaesius, R.,Fredericks, Z.,Willard, F.S.,Kuhlman, B.,Arshavsky, V.Y.,Siderovski, D.P.
Minimal Determinants for Binding Activated Galpha from the Structure of a Galpha(i1)-Peptide Dimer.
Biochemistry, 45:11390-11400, 2006

PubMed Abstract: 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 cGMP degradation. Additionally, KB-1753 interferes with RGS protein binding and resultant GAP activity. A fluorescent KB-1753 variant was found to act as a sensor for activated G alpha in vitro. The crystal structure of KB-1753 bound to G alpha(i1) x GDP x AlF4(-) reveals binding to a conserved hydrophobic groove between switch II and alpha3 helices and, along with supporting biochemical data and previous structural analyses, supports the notion that this is the site of effector interactions for G alpha(i) subunits.

PubMed: 16981699
DOI: 10.1021/bi0613832

実験手法

X-RAY DIFFRACTION (2.8 Å)