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International Conference on SARS - one year after the (first) outbreak

08. - 11.05.2004, Lübeck

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Progress in the structural and functional characterization of the coronavirus replicase complex: Crystal structure of the SARS-CoV Nsp9

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  • Marie-Pierre Egloff - University of Marseille, Marseille, France
  • François Ferron - University of Marseille, Marseille, France
  • Valérie Campanacci - University of Marseille, Marseille, France
  • Sonia Longhi - University of Marseille, Marseille, France
  • Corinne Rancurel - University of Marseille, Marseille, France
  • Hélène Dutartre - University of Marseille, Marseille, France
  • Eric J. Snijder - Leiden University Medical Center, Leiden, The Netherlands
  • Alexander E. Gorbalenya - Leiden University Medical Center, Leiden, The Netherlands
  • Christian Cambillau - University of Marseille, Marseille, France
  • corresponding author presenting/speaker Bruno Canard - University of Marseille, Marseille, France

International Conference on SARS - one year after the (first) outbreak. Lübeck, 08.-11.05.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04sars11.01

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/sars2004/04sars053.shtml

Published: May 26, 2004

© 2004 Egloff et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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In 2003, the SARS crisis has dramatically shown the scarcity of biochemical and structural data available regarding Coronaviruses. It is however anticipated that these data will greatly help anti-coronavirus drug-design, as examplified by recent work on the main protease. We are using a structural genomics approach aimed at determining the crystal structures of all the proteins encoded by the SARS-CoV genome. Currently, 28 ORFs or sub-ORFs have been targeted, and 20 proteins are in crystallization. Among those, 8 different SARS-CoV proteins, and 1 H229E-CoV have been crystallized. Here we report the crystal structure at 2.8 Å resolution of Nsp9 (113 residues), a protein from the replicase complex. Based on the crystal structure, its function has now been elucidated and awaits connection to a biological role in RNA metabolism. The crystal structure revealed that Nsp9 is a dimeric protein mainly consisting of b-strands and displaying a previously unreported overall folding resembling an OB-fold. Its partial similarity with trypsin-like proteases suggests that Nsp9 may have evolved from a protease ancestor. However, biochemical experiments support a role of Nsp9 in RNA binding, as predicted by an RNA track on the surface of the protein and relatedness with single-stranded nucleic acid binding (SSB) proteins. As this type of protein is unique in the RNA virus world, it may have a role in several processes such as recombination and the regulation of SARS-CoV replication/transcription.