Sequence analysis reveals a conserved extension in the capping enzyme of the alphavirus supergroup, and a homologous domain in nodavirusesReportar como inadecuado

Sequence analysis reveals a conserved extension in the capping enzyme of the alphavirus supergroup, and a homologous domain in nodaviruses - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Biology Direct

, 10:16

First Online: 11 April 2015Received: 29 December 2014Accepted: 24 March 2015DOI: 10.1186-s13062-015-0050-0

Cite this article as: Ahola, T. & Karlin, D.G. Biol Direct 2015 10: 16. doi:10.1186-s13062-015-0050-0


BackgroundMembers of the alphavirus supergroup include human pathogens such as chikungunya virus, hepatitis E virus and rubella virus. They encode a capping enzyme with methyltransferase-guanylyltransferase MTase-GTase activity, which is an attractive drug target owing to its unique mechanism. However, its experimental study has proven very difficult.

ResultsWe examined over 50 genera of viruses by sequence analyses. Earlier studies showed that the MTase-GTase contains a -Core- region conserved in sequence. We show that it is followed by a long extension, which we termed -Iceberg- region, whose secondary structure, but not sequence, is strikingly conserved throughout the alphavirus supergroup. Sequence analyses strongly suggest that the minimal capping domain corresponds to the Core and Iceberg regions combined, which is supported by earlier experimental data. The Iceberg region contains all known membrane association sites that contribute to the assembly of viral replication factories. We predict that it may also contain an overlooked, widely conserved membrane-binding amphipathic helix. Unexpectedly, we detected a sequence homolog of the alphavirus MTase-GTase in taxa related to nodaviruses and to chronic bee paralysis virus. The presence of a capping enzyme in nodaviruses is biologically consistent, since they have capped genomes but replicate in the cytoplasm, where no cellular capping enzyme is present. The putative MTase-GTase domain of nodaviruses also contains membrane-binding sites that may drive the assembly of viral replication factories, revealing an unsuspected parallel with the alphavirus supergroup.

ConclusionsOur work will guide the functional analysis of the alphaviral MTase-GTase and the production of domains for structure determination. The identification of a homologous domain in a simple model system, nodaviruses, which replicate in numerous eukaryotic cell systems yeast, flies, worms, mammals, and plants, can further help crack the function and structure of the enzyme.

ReviewersThis article was reviewed by Valerian Dolja, Eugene Koonin and Sebastian Maurer-Stroh.

KeywordsMethyltransferase Guanylyltransferase Capping Alphavirus Bromovirus Nodavirus Homology detection Protein sequence analysis Amphipathic alpha-helix Viral replication factory Chikungunya virus Sindbis virus Hepatitis E virus AbbreviationsaaAmino acid

BaMVBamboo mosaic virus


RdRpRNA-dependent RNA polymerase


SFVSemliki forest virus

+ssRNA virusPositive, single-stranded RNA virus

Electronic supplementary materialThe online version of this article doi:10.1186-s13062-015-0050-0 contains supplementary material, which is available to authorized users.

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Autor: Tero Ahola - David G Karlin


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