Crystal structure of a methyltransferase from a no-known-vector Flavivirus |
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Authors: | Michela Bollati Eloise Mastrangelo Xavier de Lamballerie Martino Bolognesi |
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Institution: | a Department of Biomolecular Sciences and Biotechnology, CNR-INFM and CIMAINA, University of Milano, Via Celoria 26, 20133 Milano, Italy b CNR-INFM-S3 National Research Center on Nanostructure and BioSystems at Surfaces, Via Campi 213/A, 41100 Modena, Italy c Unité des Virus Emergents, Faculté de Médecine, 27 Bd Jean Moulin, 13005 Marseille, France d Laboratoire Architecture et Fonction des Macromolécules Biologiques, UMR 6098, AFMB-CNRS-ESIL, Case 925, 163 Avenue de Luminy, 13288 Marseille, France |
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Abstract: | Presently known flaviviruses belong to three major evolutionary branches: tick-borne viruses, mosquito-borne viruses and viruses with no known vector. Here we present the crystal structure of the Yokose virus methyltransferase at 1.7 Å resolution, the first structure of a methyltransferase of a Flavivirus with no known vector. Structural comparison of three methyltransferases representative of each of the Flavivirus branches shows that fold and structures are closely conserved, most differences being related to surface loops flexibility. Analysis of the conserved residues throughout all the sequenced flaviviral methyltransferases reveals that, besides the central cleft hosting the substrate and cofactor binding sites, a second, almost continuous, patch is conserved and points away from active site towards the back of the protein. The high level of structural conservation in this region could be functional for the methyltransferase/RNA interaction and stabilization of the ensuing complex. |
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Keywords: | TBFVs tick-borne flaviviruses MBFVs mosquito-borne flaviviruses NKVs flaviviruses with no known vector NS non-structural protein MTase methyltransferase RdRp RNA-dependent-RNA polymerase AdoMet l-methionine" target="_blank">S-adenosyl-l-methionine Yv Yokose virus Dv Dengue virus Mv Meaban virus LC long construct SC short construct |
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