3FFB

Gi-alpha-1 mutant in GDP bound form

3FFB の概要

• エントリーDOI: 10.2210/pdb3ffb/pdb
• 関連するPDBエントリー: 3FFA
• 分子名称: Guanine nucleotide-binding protein G(i), alpha-1 subunit, GUANOSINE-5'-DIPHOSPHATE, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: gi-alpha-1 fast activating mutant, gtp-binding, lipoprotein, myristate, nucleotide-binding, palmitate, transducer, signal transduction, signaling protein
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats)
• 細胞内の位置: Nucleus: P10824
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41489.94

構造登録者

Chauhan, R.,Kapoor, N. (登録日: 2008-12-02, 公開日: 2009-10-06, 最終更新日: 2023-09-06)

主引用文献

Kapoor, N.,Menon, S.T.,Chauhan, R.,Sachdev, P.,Sakmar, T.P.
Structural evidence for a sequential release mechanism for activation of heterotrimeric g proteins.
J.Mol.Biol., 393:882-897, 2009

PubMed Abstract: Heptahelical G-protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors couple to heterotrimeric G proteins to relay extracellular signals to intracellular signaling networks, but the molecular mechanism underlying guanosine 5'-diphosphate (GDP) release by the G protein alpha-subunit is not well understood. Amino acid substitutions in the conserved alpha5 helix of G(i), which extends from the C-terminal region to the nucleotide-binding pocket, cause dramatic increases in basal (receptor-independent) GDP release rates. For example, mutant Galpha(i1)-T329A shows an 18-fold increase in basal GDP release rate and, when expressed in culture, it causes a significant decrease in forskolin-stimulated cAMP accumulation. The crystal structure of Galpha(i1)-T329A.GDP shows substantial conformational rearrangement of the switch I region and additional striking alterations of side chains lining the catalytic pocket that disrupt the Mg(+2) coordination sphere and dislodge bound Mg(+2). We propose a "sequential release" mechanism whereby a transient conformational change in the alpha5 helix alters switch I to induce GDP release. Interestingly, this mechanistic model for heterotrimeric G protein activation is similar to that suggested for the activation of the plant small G protein Rop4 by RopGEF8.

PubMed: 19703466
DOI: 10.1016/j.jmb.2009.08.043

実験手法

X-RAY DIFFRACTION (2.57 Å)