Solution structure of the N-terminal extension domain of a Schistosoma japonicum asparaginyl-tRNA synthetase

Peck, Yoshimi, Pickering, Darren, Mobli, Mehdi, Liddell, Michael J., Wilson, David T, Ruscher, Roland, Ryan, Stephanie, Buitrago, Geraldine, McHugh, Connor, Love, Nicholas C., Pinlac, Theresa, Haertlein, Michael, Kron, Michael A., Loukas, Alex, and Daly, Norelle L. (2024) Solution structure of the N-terminal extension domain of a Schistosoma japonicum asparaginyl-tRNA synthetase. Journal of Biomolecular Structure and Dynamics. (In Press)

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Abstract

Several secreted proteins from helminths (parasitic worms) have been shown to have immunomodulatory activities. Asparaginyl-tRNA synthetases are abundantly secreted in the filarial nematode Brugia malayi (BmAsnRS) and the parasitic flatworm Schistosoma japonicum (SjAsnRS), indicating a possible immune function. The suggestion is supported by BmAsnRS alleviating disease symptoms in a T-cell transfer mouse model of colitis. This immunomodulatory function is potentially related to an N-terminal extension domain present in eukaryotic AsnRS proteins but few structure/function studies have been done on this domain. Here we have determined the three-dimensional solution structure of the N-terminal extension domain of SjAsnRS. A protein containing the 114 N-terminal amino acids of SjAsnRS was recombinantly expressed with isotopic labelling to allow structure determination using 3D NMR spectroscopy, and analysis of dynamics using NMR relaxation experiments. Structural comparisons of the N-terminal extension domain of SjAsnRS with filarial and human homologues highlight a high degree of variability in the β-hairpin region of these eukaryotic N-AsnRS proteins, but similarities in the disorder of the C-terminal regions. Limitations in PrDOS-based intrinsically disordered region (IDR) model predictions were also evident in this comparison. Empirical structural data such as that presented in our study for N-SjAsnRS will enhance the prediction of sequence-homology based structure modelling and prediction of IDRs in the future.

Item ID: 80378
Item Type: Article (Research - C1)
ISSN: 1538-0254
Keywords: 15 N relaxation, 3D NMR, intrinsically disordered region (IDR), N-terminal extension, parasitic worm, tRNA synthetase, β-hairpin
Copyright Information: © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
Funders: Australian Research Council (ARC)
Projects and Grants: ARC LE160100218
Date Deposited: 26 Feb 2024 23:41
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320704 Medical parasitology @ 100%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 100%
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