3T5I

Structure of Fully modified farnesylated Rheb Peptide in complex with PDE6D

3T5I の概要

• エントリーDOI: 10.2210/pdb3t5i/pdb
• 関連するPDBエントリー: 3T5G
• 分子名称: Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta, C-terminal Farnesylated Rheb peptide CSQQGKSS(CMT), FARNESYL, ... (4 entities in total)
• 機能のキーワード: immunoglobulin-like beta sandwitch fold, rheb, farnesyl, prenyl, signaling protein, lipid binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, cytosol : O43924
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 73050.05

構造登録者

Ismail, S.A.,Chen, Y.-X.,Wittinghofer, A. (登録日: 2011-07-27, 公開日: 2011-11-02, 最終更新日: 2023-09-13)

主引用文献

Ismail, S.A.,Chen, Y.X.,Rusinova, A.,Chandra, A.,Bierbaum, M.,Gremer, L.,Triola, G.,Waldmann, H.,Bastiaens, P.I.,Wittinghofer, A.
Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo.
Nat.Chem.Biol., 7:942-949, 2011

PubMed Abstract: Lipidated Rho and Rab GTP-binding proteins are transported between membranes in complex with solubilizing factors called 'guanine nucleotide dissociation inhibitors' (GDIs). Unloading from GDIs using GDI displacement factors (GDFs) has been proposed but remains mechanistically elusive. PDEδ is a putative solubilizing factor for several prenylated Ras-subfamily proteins. Here we report the structure of fully modified farnesylated Rheb-GDP in complex with PDEδ. The structure explains the nucleotide-independent binding of Rheb to PDEδ and the relaxed specificity of PDEδ. We demonstrate that the G proteins Arl2 and Arl3 act in a GTP-dependent manner as allosteric release factors for farnesylated cargo. We thus describe a new transport system for farnesylated G proteins involving a GDI-like molecule and an unequivocal GDF. Considering the importance of PDEδ for proper Ras and Rheb signaling, this study is instrumental in developing a new target for anticancer therapy.

PubMed: 22002721
DOI: 10.1038/nchembio.686

実験手法

X-RAY DIFFRACTION (2.1 Å)