Sequence-specific backbone resonance assignments and microsecond timescale molecular dynamics simulation of human eosinophil-derived neurotoxin
- 207 Downloads
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.
KeywordsRibonucleases RNA RNase A EDN RNase 2 Protein orthologs Enzyme dynamics
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.
- Case D, Babin V, Berryman J, Betz R, Cai Q, Cerutti D et al. (2014) Amber 14, University of California, San FranciscoGoogle Scholar
- Hamann KJ, Gleich GJ, Checkel JL, Loegering DA, McCall JW, Barker RL (1990) In vitro killing of microfilariae of Brugia pahangi and Brugia malayi by eosinophil granule proteins. J Immunol 144:3166–3173Google Scholar
- Lehrer RI, Szklarek D, Barton A, Ganz T, Hamann KJ, Gleich GJ (1989) Antibacterial properties of eosinophil major basic protein and eosinophil cationic protein. J Immunol 142:4428–4434Google Scholar
- Slifman NR, Loegering DA, McKean DJ, Gleich GJ (1986) Ribonuclease activity associated with human eosinophil-derived neurotoxin and eosinophil cationic protein. J Immunol 137:2913–2917Google Scholar
- Wilkins MR, Gasteiger E, Bairoch A, Sanchez JC, Williams KL, Appel RD et al (1999) Protein identification and analysis tools in the ExPASy server. Methods Mol Biol 112:531–552Google Scholar