3VGJ

Crystal of Plasmodium falciparum tyrosyl-tRNA synthetase (PfTyrRS)in complex with adenylate analog

3VGJ の概要

• エントリーDOI: 10.2210/pdb3vgj/pdb
• 関連するPDBエントリー: 1N3L 1Q11
• 分子名称: Tyrosyl-tRNA synthetase, putative, TYROSINE, ADENOSINE MONOPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: tyrrs, synthetase, ligase
• 由来する生物種: Plasmodium falciparum
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 88085.27

構造登録者

Banday, M.M.,Yogavel, M.,Bhatt, T.K.,Khan, S.,Sharma, A.,Sharma, A. (登録日: 2011-08-14, 公開日: 2012-07-25, 最終更新日: 2024-03-20)

主引用文献

Bhatt, T.K.,Khan, S.,Dwivedi, V.P.,Banday, M.M.,Sharma, A.,Chandele, A.,Camacho, N.,de Pouplana, L.R.,Wu, Y.,Craig, A.G.,Mikkonen, A.T.,Maier, A.G.,Yogavel, M.,Sharma, A.
Malaria parasite tyrosyl-tRNA synthetase secretion triggers pro-inflammatory responses.
Nat Commun, 2:530-530, 2011

PubMed Abstract: Malaria infection triggers pro-inflammatory responses in humans that are detrimental to host health. Parasite-induced enhancement in cytokine levels correlate with malaria-associated pathologies. Here we show that parasite tyrosyl-tRNA synthetase (PfTyrRS), a housekeeping protein translation enzyme, induces pro-inflammatory responses from host immune cells. PfTyrRS exits from the parasite cytoplasm into the infected red blood cell (iRBC) cytoplasm, from where it is released into the extracellular medium on iRBC lysis. Using its ELR peptide motif, PfTyrRS specifically binds to and internalizes into host macrophages, leading to enhanced secretion of the pro-inflammatory cytokines TNF-α and IL-6. PfTyrRS-macrophage interaction also augments expression of adherence-linked host endothelial receptors ICAM-1 and VCAM-1. Our description of PfTyrRS as a parasite-secreted protein that triggers pro-inflammatory host responses, along with its atomic resolution crystal structure in complex with tyrosyl-adenylate, provides a novel platform for targeting PfTyrRS in anti-parasitic strategies.

PubMed: 22068597
DOI: 10.1038/ncomms1522

実験手法

X-RAY DIFFRACTION (2.212 Å)