4ZYA

The N-terminal extension domain of human asparaginyl-tRNA synthetase

4ZYA の概要

• エントリーDOI: 10.2210/pdb4zya/pdb
• 関連するPDBエントリー: 4ZWF
• 分子名称: Asparagine--tRNA ligase, cytoplasmic, ZINC ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: asparaginyl-trna synthetase, ligase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18351.75

構造登録者

Park, J.S.,Park, M.C.,Goughnour, P.,Kim, H.S.,Kim, S.J.,Kim, H.J.,Kim, S.H.,Han, B.W. (登録日: 2015-05-21, 公開日: 2016-05-25, 最終更新日: 2024-10-16)

主引用文献

Park, J.S.,Park, M.C.,Lee, K.Y.,Goughnour, P.C.,Jeong, S.J.,Kim, H.S.,Kim, H.J.,Lee, B.J.,Kim, S.,Han, B.W.
Unique N-terminal extension domain of human asparaginyl-tRNA synthetase elicits CCR3-mediated chemokine activity.
Int. J. Biol. Macromol., 120:835-845, 2018

PubMed Abstract: Asparaginyl-tRNA synthetase (NRS) is not only essential in protein translation but also associated with autoimmune diseases. Particularly, patients with antibodies that recognize NRS often develop interstitial lung disease (ILD). However, the underlying mechanism of how NRS is recognized by immune cells and provokes inflammatory responses is not well-understood. Here, we found that the crystal structure of the unique N-terminal extension domain of human NRS (named as UNE-N, where -N denotes NRS) resembles that of the chemotactic N-terminal domain of NRS from a filarial nematode, Brugia malayi, which recruits and activates specific immune cells by interacting with CXC chemokine receptor 1 and 2. UNE-N induced migration of CC chemokine receptor 3 (CCR3)-expressing cells. The chemokine activity of UNE-N was significantly reduced by suppressing CCR3 expression with CCR3-targeting siRNA, and the loop3 region of UNE-N was shown to interact mainly with the extracellular domains of CCR3 in nuclear magnetic resonance perturbation experiments. Based on these results, evolutionarily acquired UNE-N elicits chemokine activities that would promote NRS-CCR3-mediated proinflammatory signaling in ILD.

PubMed: 30171954
DOI: 10.1016/j.ijbiomac.2018.08.171

実験手法

X-RAY DIFFRACTION (1.65 Å)