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Sequence-specific backbone resonance assignments and microsecond timescale molecular dynamics simulation of human eosinophil-derived neurotoxin

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A Correction to this article was published on 06 August 2018

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Abstract

Eight active canonical members of the pancreatic-like ribonuclease A (RNase A) superfamily have been identified in human. All structural homologs share similar RNA-degrading functions, while also cumulating other various biological activities in different tissues. The functional homologs eosinophil-derived neurotoxin (EDN, or RNase 2) and eosinophil cationic protein (ECP, or RNase 3) are known to be expressed and secreted by eosinophils in response to infection, and have thus been postulated to play an important role in host defense and inflammatory response. We recently initiated the biophysical and dynamical investigation of several vertebrate RNase homologs and observed that clustering residue dynamics appear to be linked with the phylogeny and biological specificity of several members. Here we report the 1H, 13C and 15N backbone resonance assignments of human EDN (RNase 2) and its molecular dynamics simulation on the microsecond timescale, providing means to pursue this comparative atomic-scale functional and dynamical analysis by NMR and computation over multiple time frames.

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Change history

  • 06 August 2018

    After publication of this article, the authors noticed that a 15N–13C dimension error was unwillingly coded in the 3D NMR spectrum “fid.com” processing script used to perform backbone assignments for this enzyme. The authors noticed that some OBS, CAR and LAB values in the “fid.com” had been switched in the y and z dimensions, probably resulting from a wrong NMRPipe selection when reading the Varian NMR experimental parameters. They have carefully re-processed, re-analyzed, re-assigned, in addition to checking all scripts to evaluate the extent of this processing error on the published assignments. Authors determined that the “fid.com” error resulted in a significant number of incorrect backbone resonance assignments, requiring us to issue corrections in Figs. 2, 3 and 4 of this published manuscript, in addition to Table S1. New versions of these figures and table are provided below. The corresponding BMRB entry has also been revised. The authors note that these modifications do not change the global message, conclusions, and molecular dynamics simulations presented in this article. The authors are grateful to David N. Bernard (INRS) for help with finding and correcting these errors.

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Acknowledgements

The authors thank Tara Sprules (Québec/Eastern Canada High Field NMR Facility, McGill University) and Sameer Al-Abdul-Wahid (NMR Centre, University of Guelph) for their excellent technical assistance, in addition to David Bernard (INRS-Institut Armand-Frappier) and Bruce Johnson (CUNY Advanced Science Research Center) for helpful discussions. This work was supported by the National Institute of General Medical Sciences (NIGMS) of the NIH under award number R01GM105978 (to N.D. and P.K.A.), and a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant under award number RGPIN-2016-05557 (to N. D.). N.D. holds a Fonds de Recherche Québec – Santé (FRQS) Research Scholar Junior 2 Career Award. C.N. is the recipient of a postdoctoral fellowship from the Fondation Universitaire Armand-Frappier de l’INRS. D.G. and L.A.C. were respectively recipients of an NSERC Alexander Graham Bell Canada Graduate Scholarship and a M.Sc. scholarship from the Fondation Universitaire Armand-Frappier de l’INRS.

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Author notes

  1. Donald Gagné

    Present address: Structural Biology Initiative, CUNY Advanced Science Research Center, New York, NY, 10031, USA

Authors and Affiliations

  1. INRS-Institut Armand-Frappier, Université du Québec, 531 Boulevard des Prairies, Laval, QC, H7V 1B7, Canada

    Donald Gagné, Chitra Narayanan, Laurie-Anne Charest & Nicolas Doucet

  2. Graduate School of Genome Science and Technology, University of Tennessee, Knoxville, TN, 37996, USA

    Khushboo Bafna

  3. Computational Biology Institute and Computer Science and Mathematics Division, Oak Ridge National Laboratory, 1 Bethel Valley Road, Oak Ridge, TN, 37830, USA

    Pratul K. Agarwal

  4. Department of Biochemistry, Cellular and Molecular Biology, University of Tennessee, Knoxville, TN, 37996, USA

    Pratul K. Agarwal

  5. PROTEO, The Québec Network for Research on Protein Function, Engineering, and Applications, Université Laval, 1045 Avenue de la Médecine, Quebec, QC, G1V 0A6, Canada

    Nicolas Doucet

  6. GRASP, The Groupe de recherche Axé sur la Structure des Protéines, McGill University, 3649 Promenade Sir William Osler, Montreal, QC, H3G 0B1, Canada

    Nicolas Doucet

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  1. Donald Gagné
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Correspondence to Nicolas Doucet.

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Gagné, D., Narayanan, C., Bafna, K. et al. Sequence-specific backbone resonance assignments and microsecond timescale molecular dynamics simulation of human eosinophil-derived neurotoxin. Biomol NMR Assign 11, 143–149 (2017). https://doi.org/10.1007/s12104-017-9736-9

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