3B21

Crystal structure of OspI from Shigella flexineri

3B21 の概要

• エントリーDOI: 10.2210/pdb3b21/pdb
• 分子名称: ORF169b (2 entities in total)
• 機能のキーワード: shigella, bacterial protein, effector, type 3 secretion system, unknown function
• 由来する生物種: Shigella flexneri
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24150.87

構造登録者

Sanada, T.,Kim, M.,Sasakawa, C.,Mizushima, T. (登録日: 2011-07-19, 公開日: 2012-02-22, 最終更新日: 2024-10-23)

主引用文献

Sanada, T.,Kim, M.,Mimuro, H.,Suzuki, M.,Ogawa, M.,Oyama, A.,Ashida, H.,Kobayashi, T.,Koyama, T.,Nagai, S.,Shibata, Y.,Gohda, J.,Inoue, J.I.,Mizushima, T.,Sasakawa, C.
The Shigella flexneri effector OspI deamidates UBC13 to dampen the inflammatory response
Nature, 483:623-626, 2012

PubMed Abstract: Many bacterial pathogens can enter various host cells and then survive intracellularly, transiently evade humoral immunity, and further disseminate to other cells and tissues. When bacteria enter host cells and replicate intracellularly, the host cells sense the invading bacteria as damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) by way of various pattern recognition receptors. As a result, the host cells induce alarm signals that activate the innate immune system. Therefore, bacteria must modulate host inflammatory signalling and dampen these alarm signals. How pathogens do this after invading epithelial cells remains unclear, however. Here we show that OspI, a Shigella flexneri effector encoded by ORF169b on the large plasmid and delivered by the type ΙΙΙ secretion system, dampens acute inflammatory responses during bacterial invasion by suppressing the tumour-necrosis factor (TNF)-receptor-associated factor 6 (TRAF6)-mediated signalling pathway. OspI is a glutamine deamidase that selectively deamidates the glutamine residue at position 100 in UBC13 to a glutamic acid residue. Consequently, the E2 ubiquitin-conjugating activity required for TRAF6 activation is inhibited, allowing S. flexneri OspI to modulate the diacylglycerol-CBM (CARD-BCL10-MALT1) complex-TRAF6-nuclear-factor-κB signalling pathway. We determined the 2.0 Å crystal structure of OspI, which contains a putative cysteine-histidine-aspartic acid catalytic triad. A mutational analysis showed this catalytic triad to be essential for the deamidation of UBC13. Our results suggest that S. flexneri inhibits acute inflammatory responses in the initial stage of infection by targeting the UBC13-TRAF6 complex.

PubMed: 22407319
DOI: 10.1038/nature10894

実験手法

X-RAY DIFFRACTION (2.01 Å)