2OT3

Crystal structure of rabex-5 VPS9 domain in complex with nucleotide free RAB21

2OT3 の概要

• エントリーDOI: 10.2210/pdb2ot3/pdb
• 関連するPDBエントリー: 1TXU 1Z0I
• 分子名称: Rab5 GDP/GTP exchange factor, Ras-related protein Rab-21 (3 entities in total)
• 機能のキーワード: rabex-5, vps9 domain, rab21, vesicular traffic, protein transport
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm : Q9UJ41; Endoplasmic reticulum membrane ; Lipid-anchor : Q9UL25
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51418.00

構造登録者

Delprato, A.,Lambright, D. (登録日: 2007-02-07, 公開日: 2007-04-24, 最終更新日: 2023-08-30)

主引用文献

Delprato, A.,Lambright, D.G.
Structural basis for Rab GTPase activation by VPS9 domain exchange factors.
Nat.Struct.Mol.Biol., 14:406-412, 2007

PubMed Abstract: RABEX-5 and other exchange factors with VPS9 domains regulate endocytic trafficking through activation of the Rab family GTPases RAB5, RAB21 and RAB22. Here we report the crystal structure of the RABEX-5 catalytic core in complex with nucleotide-free RAB21, a key intermediate in the exchange reaction pathway. The structure reveals how VPS9 domain exchange factors recognize Rab GTPase substrates, accelerate GDP release and stabilize the nucleotide-free conformation. We further identify an autoinhibitory element in a predicted amphipathic helix located near the C terminus of the VPS9 domain. The autoinhibitory element overlaps with the binding site for the multivalent effector RABAPTIN-5 and potently suppresses the exchange activity of RABEX-5. Autoinhibition can be partially reversed by mutation of conserved residues on the nonpolar face of the predicted amphipathic helix or by assembly of the complex with RABAPTIN-5.

PubMed: 17450153
DOI: 10.1038/nsmb1232

実験手法

X-RAY DIFFRACTION (2.1 Å)