5OEC

Human Rab32 (18-201):GDP in complex with Salmonella GtgE (21-214) C45A mutant

5OEC の概要

• エントリーDOI: 10.2210/pdb5oec/pdb
• 関連するPDBエントリー: 4CYM 4MI7
• 分子名称: GtgE, Ras-related protein Rab-32, GUANOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: rab gtpase, posttranslational modification, proteolysis, salmonella infection, hydrolase
• 由来する生物種: Salmonella choleraesuis; 詳細
• 細胞内の位置: Mitochondrion : Q13637
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44010.45

構造登録者

Wachtel, R.,Braeuning, B.,Mader, S.L.,Ecker, F.,Kaila, V.R.I.,Groll, M.,Itzen, A. (登録日: 2017-07-07, 公開日: 2018-01-10, 最終更新日: 2024-01-17)

主引用文献

Wachtel, R.,Brauning, B.,Mader, S.L.,Ecker, F.,Kaila, V.R.I.,Groll, M.,Itzen, A.
The protease GtgE from Salmonella exclusively targets inactive Rab GTPases.
Nat Commun, 9:44-44, 2018

PubMed Abstract: Salmonella infections require the delivery of bacterial effectors into the host cell that alter the regulation of host defense mechanisms. The secreted cysteine protease GtgE from S. Typhimurium manipulates vesicular trafficking by modifying the Rab32 subfamily via cleaving the regulatory switch I region. Here we present a comprehensive biochemical, structural, and computational characterization of GtgE in complex with Rab32. Interestingly, GtgE solely processes the inactive GDP-bound GTPase. The crystal structure of the Rab32:GDP substrate in complex with the inactive mutant GtgE reveals the molecular basis of substrate recognition. In combination with atomistic molecular dynamics simulations, the structural determinants for protein and activity-state specificity are identified. Mutations in a central interaction hub lead to loss of the strict GDP specificity. Our findings shed light on the sequence of host cell manipulation events during Salmonella infection and provide an explanation for the dependence on the co-secreted GTPase activating protein SopD2.

PubMed: 29298974
DOI: 10.1038/s41467-017-02110-1

実験手法

X-RAY DIFFRACTION (2.3 Å)