Atlas of coronavirus replicase structure

Abstract

The international response to SARS-CoV has produced an outstanding number of protein structures in a very short time. This review summarizes the findings of functional and structural studies including those derived from cryoelectron microscopy, small angle X-ray scattering, NMR spectroscopy, and X-ray crystallography, and incorporates bioinformatics predictions where no structural data is available. Structures that shed light on the function and biological roles of the proteins in viral replication and pathogenesis are highlighted. The high percentage of novel protein folds identified among SARS-CoV proteins is discussed.

Keywords: Cryoelectron microscopy; NMR; Nonstructural protein; Protein structure; SARS coronavirus; Small angle X-ray scattering; X-ray crystallography.

Fig. 1

Conservation of the SARS-CoV replicase. Replicase subunits, or domains for nsp3, were color-coded according to percent identity between homologous proteins of SARS-CoV and MERS-CoV. Alignments and identity calculations were performed using Clustal Omega (Sievers et al., 2011).

Fig. 2

Comparison of nsp1 structure in alpha- and betacoronavirus lineages. The SARS-CoV nsp1 structure comes from PDB entry 2HSX, and the TGEV nsp1 structure comes from PDB entry 3ZBD.

Fig. 3

Bioinformatics detection of homology and domain organization in nsp2. The structure of IBV nsp2 is taken from PDB entry 3LD1. Predicted secondary structures for representative coronavirus lineages were made by PsiPRED 3.0 (McGuffin et al., 2000). Rectangles represent α-helices and arrows represent beta-strands.

Fig. 4

Domain architecture and structure of the conserved DMV-making proteins nsp3 through nsp6. A partially schematic view combining the known domain structures of SARS-CoV nsp3 is shown in panel A, combining the PDB entries 2IDY, 2ACF, 2FE8, 2KAF, 2JZF, 2W2G and 2K87. Conservation of structural domains and other important sequence features is shown for four representative coronaviruses in panel B. Structures of the C-terminal domain of FCoV nsp4 (3GZF), SARS-CoV nsp5 (1UJ1), TGEV nsp5 (1LVO) and IBV nsp5 (2Q6F) are shown in panels C–F, respectively.

Fig. 5

Structures of the coronavirus replicase proteins nsp7, nsp8 and nsp9. Structures for the nsp7 and nsp8 heterodimers from SARS-CoV (2AHM; panel A) and FCoV (3UB0; panel B) are shown to illustrate the distinctive structures of these proteins. The structure of homodimeric SARS-CoV nsp9 is taken from PDB entry 1QZ8 and is shown in panel C.

Fig. 6

Structures of the replicase proteins nsp10, 15 and 16. The hexameric structure of SARS-CoV nsp15 comes from PDB entry 2H85 and is shown in panel A. The structure of the SARS-CoV nsp10–16 shown in panel B complex is taken from PDB entry 2XYQ (nsp10 is shown on the left).