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The active form of the norovirus RNA-dependent RNA polymerase is a homodimer with cooperative activity

Martin Högbom^1,

Katrin Jäger^2,

¹ Stockholm Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
² Institut für Virologie, The Calicilab, Medizinisch-Theoretisches Zentrum, Dresden, Germany
³ Institute of Cell and Molecular Biology, Uppsala University, Sweden

Correspondence
Jacques Rohayem
Jacques.Rohayem{at}mailbox.tu-dresden.de

Norovirus (NV) is a leading cause of gastroenteritis worldwide and a major public health concern. So far, the replication strategy of NV remains poorly understood, mainly because of the lack of a cell system to cultivate the virus. In this study, the function and the structure of a key viral enzyme of replication, the RNA-dependent RNA polymerase (RdRp, NS7), was examined. The overall structure of the NV NS7 RdRp was determined by X-ray crystallography to a 2.3 Å (0.23 nm) resolution (PDB ID 2B43), displaying a right-hand fold typical of the template-dependent polynucleotide polymerases. Biochemical analysis evidenced that NV NS7 RdRp is active as a homodimer, with an apparent K_d of 0.649 µM and a positive cooperativity (Hill coefficient n_H=1.86). Crystals of the NV NS7 homodimer displayed lattices containing dimeric arrangements with high shape complementarity statistics. This experimental data on the structure and function of the NV RdRp may set the cornerstone for the development of polymerase inhibitors to control the infection with NV, a medically relevant pathogen.

These authors contributed equally to this work.

Published online ahead of print on 7 November 2008 as DOI 10.1099/vir.0.005629-0