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

Autor:	Peck Y; Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia., Pickering D; Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia., Mobli M; Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, Australia., Liddell MJ; College of Science and Engineering, James Cook University, Cairns, QLD, Australia., Wilson DT; Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia., Ruscher R; Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia., Ryan S; Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia., Buitrago G; Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK., McHugh C; Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia., Love NC; Medical College of Wisconsin, Milwaukee, WI, USA., Pinlac T; Department of Biochemistry, University of the Philippines, Manila, Philippines., Haertlein M; Deuteration Laboratory, Institut Laue-Langevin, Grenoble, France., Kron MA; Department of Medicine, Division of Infectious Diseases, Medical College of Wisconsin, Milwaukee, WI, USA., Loukas A; Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia., Daly NL; Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.
Jazyk:	angličtina
Zdroj:	Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2024 Sep; Vol. 42 (15), pp. 7934-7944. Date of Electronic Publication: 2023 Aug 12.
DOI:	10.1080/07391102.2023.2241918
Abstrakt:	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 ( Bm AsnRS) and the parasitic flatworm Schistosoma japonicum ( Sj AsnRS), indicating a possible immune function. The suggestion is supported by Bm AsnRS 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 Sj AsnRS. A protein containing the 114 N-terminal amino acids of Sj AsnRS 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 Sj AsnRS 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- Sj AsnRS will enhance the prediction of sequence-homology based structure modelling and prediction of IDRs in the future.Communicated by Ramaswamy H. Sarma.
Databáze:	MEDLINE
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