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Figure 5.
Figure 5. The Structural Evolution of Alternative Open
Reading Frames in Viruses
(A) The evolution of
coronaviruses (adapted from Snijder et al., 2003). Based on
their genome sequence, coronaviruses fall into three main
groups. SARS-CoV is thought to be an early split-off from the
group 2 lineage (indicated by a dashed circle). Alternative open
reading frames of the nucleocapsid gene are found only in group
2 viruses, such as MHV and BCV (Senanayake and Brian, 1997), as
well as group 2-related viruses, including SARS-CoV. BCV, bovine
coronavirus; HCoV-229E, human coronavirus 229E; IBV, infectious
bronchitis virus; MHV, murine hepatitis virus; PDEV, porcine
epidemic diarrhea virus; SARS-CoV, severe acute respiratory
syndrome coronavirus; TGEV, transmissible gastroenteritis virus.
(B) A model for the structural evolution of ORF-9b within
the SARS-CoV N-gene. Starting from an N-gene without an
alternative ORF, the protein first arises as an “accidental”
translation product, which is mostly unstructured. By gradual
constrained evolution, it becomes increasingly structured,
eventually attaining its present fold. In this scheme,
disordered regions (colored in red) are a relict of the
evolutionary trajectory of the protein. The N-protein is
represented as a composite of two NMR structures of its
well-conserved N- and C-terminal domains ([Chang et al., 2005a]
and [Huang et al., 2004]), which are thought to be surrounded by
flexible linkers (Chang et al., 2005b) (colored in red). The
region of the N-terminal domain which overlaps with ORF-9b is
shown in green.
(C) For comparison, an illustration of the
HIV1 vpu and env genes, which partially overlap. The NMR
structure of the overlapping portion of VPU (Willbold et al.,
1997) (PDB code: 1VPU) is shown. This protein is relatively
poorly ordered (rmsd = 1.6 Å between multiple
determinations of the fold, for all Cα atoms). The least
ordered regions (rmsd > 2 Å) are highlighted in red.
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