4IIK

Legionella pneumophila effector

4IIK の概要

• エントリーDOI: 10.2210/pdb4iik/pdb
• 関連するPDBエントリー: 4IIP
• 分子名称: Adenosine monophosphate-protein hydrolase SidD, MAGNESIUM ION, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: beta sandwich, de-ampylation, rab1, legionella containing vacuole surface, hydrolase
• 由来する生物種: Legionella pneumophila
• 細胞内の位置: Host cytoplasm, host perinuclear region: Q5ZSQ2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36951.67

構造登録者

Tascon, I.,Chen, Y.,Neunuebel, M.R.,Rojas, A.L.,Machner, M.P.,Hierro, A. (登録日: 2012-12-20, 公開日: 2013-06-19, 最終更新日: 2024-03-20)

主引用文献

Chen, Y.,Tascon, I.,Neunuebel, M.R.,Pallara, C.,Brady, J.,Kinch, L.N.,Fernandez-Recio, J.,Rojas, A.L.,Machner, M.P.,Hierro, A.
Structural Basis for Rab1 De-AMPylation by the Legionella pneumophila Effector SidD
Plos Pathog., 9:e1003382-e1003382, 2013

PubMed Abstract: The covalent attachment of adenosine monophosphate (AMP) to proteins, a process called AMPylation (adenylylation), has recently emerged as a novel theme in microbial pathogenesis. Although several AMPylating enzymes have been characterized, the only known virulence protein with de-AMPylation activity is SidD from the human pathogen Legionella pneumophila. SidD de-AMPylates mammalian Rab1, a small GTPase involved in secretory vesicle transport, thereby targeting the host protein for inactivation. The molecular mechanisms underlying Rab1 recognition and de-AMPylation by SidD are unclear. Here, we report the crystal structure of the catalytic region of SidD at 1.6 Å resolution. The structure reveals a phosphatase-like fold with additional structural elements not present in generic PP2C-type phosphatases. The catalytic pocket contains a binuclear metal-binding site characteristic of hydrolytic metalloenzymes, with strong dependency on magnesium ions. Subsequent docking and molecular dynamics simulations between SidD and Rab1 revealed the interface contacts and the energetic contribution of key residues to the interaction. In conjunction with an extensive structure-based mutational analysis, we provide in vivo and in vitro evidence for a remarkable adaptation of SidD to its host cell target Rab1 which explains how this effector confers specificity to the reaction it catalyses.

PubMed: 23696742
DOI: 10.1371/journal.ppat.1003382

実験手法

X-RAY DIFFRACTION (1.6 Å)