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 C–C 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.
|Number of pages||11|
|Journal||International Journal of Biological Macromolecules|
|Publication status||Published - 2018 Dec|
Bibliographical noteFunding Information:
This work was supported by the Global Frontier Project (grants number: NRF-2013M-3A6A-4043695) and Tumor Microenvironment Global Core Research Center (grant number: 2011-0030001) funded through the National Research Foundation from the Ministry of Science and ICT of Korea.
This work was supported by the Global Frontier Project (grants number: NRF- 2013M-3A6A-4043695 ) and Tumor Microenvironment Global Core Research Center (grant number: 2011-0030001 ) funded through the National Research Foundation from the Ministry of Science and ICT of Korea.
© 2018 Elsevier B.V.
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Biology
- Economics and Econometrics