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Publication Abstract from PubMed

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 beta-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.Communicated by Ramaswamy H. Sarma.

Solution structure of the N-terminal extension domain of a Schistosoma japonicum asparaginyl-tRNA synthetase.,Peck Y, Pickering D, Mobli M, Liddell MJ, Wilson DT, Ruscher R, Ryan S, Buitrago G, McHugh C, Love NC, Pinlac T, Haertlein M, Kron MA, Loukas A, Daly NL J Biomol Struct Dyn. 2023 Aug 12:1-11. doi: 10.1080/07391102.2023.2241918. PMID:37572327^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.