4O25

Structure of Wild Type Mus musculus Rheb bound to GTP

4O25 の概要

• エントリーDOI: 10.2210/pdb4o25/pdb
• 関連するPDBエントリー: 4O2L 4O2R
• 分子名称: GTP-binding protein Rheb, GUANOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: small gtpase, hydrolase, gtp and gdp
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Cell membrane ; Lipid-anchor ; Cytoplasmic side : Q921J2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 39482.83

構造登録者

Mazhab-Jafari, M.T.,Marshall, C.B.,Ho, J.,Ishiyama, N.,Stambolic, V.,Ikura, M. (登録日: 2013-12-16, 公開日: 2014-03-26, 最終更新日: 2024-02-28)

主引用文献

Mazhab-Jafari, M.T.,Marshall, C.B.,Ho, J.,Ishiyama, N.,Stambolic, V.,Ikura, M.
Structure-guided mutation of the conserved G3-box glycine in Rheb generates a constitutively activated regulator of mammalian target of rapamycin (mTOR).
J.Biol.Chem., 289:12195-12201, 2014

PubMed Abstract: Constitutively activated variants of small GTPases, which provide valuable functional probes of their role in cellular signaling pathways, can often be generated by mutating the canonical catalytic residue (e.g. Ras Q61L) to impair GTP hydrolysis. However, this general approach is ineffective for a substantial fraction of the small GTPase family in which this residue is not conserved (e.g. Rap) or not catalytic (e.g. Rheb). Using a novel engineering approach, we have manipulated nucleotide binding through structure-guided substitutions of an ultraconserved glycine residue in the G3-box motif (DXXG). Substitution of Rheb Gly-63 with alanine impaired both intrinsic and TSC2 GTPase-activating protein (GAP)-mediated GTP hydrolysis by displacing the hydrolytic water molecule, whereas introduction of a bulkier valine side chain selectively blocked GTP binding by steric occlusion of the γ-phosphate. Rheb G63A stimulated phosphorylation of the mTORC1 substrate p70S6 kinase more strongly than wild-type, thus offering a new tool for mammalian target of rapamycin (mTOR) signaling.

PubMed: 24648513
DOI: 10.1074/jbc.C113.543736

実験手法

X-RAY DIFFRACTION (2.2 Å)