A structure of the Sindis virus capsid
Michael Rossmann group (Purdue University) and colleagues
Alphaviruses are a group of lipid-membrane-enveloped
viruses, many of which are significant human pathogens, including Chikungunya
virus and Venezuelan equine encephalitis virus. However, there are currently
no anti-viral drugs or vaccines available for these viruses. Detailed
information of the virus structures and life cycles would greatly help the
design and development of anti-viral strategies. Alphaviruses have two
glycoproteins, E1 and E2, covering the virion surface. Both play critical
roles in attaining virus entry into host cells. The E1 protein mediates
fusion of the viral membrane with the endosomal membrane of host cells in the
acidic environment. The E2 protein recognizes molecules on the viral surface
that can act as receptors on the cellular surface to initiate virus entry.
Michael Rossmann and colleagues determined the crystal structure of the E1-E2
protein from Sindbis virus, a commonly used laboratory alphavirus. The
structure of E1 was previously known and was used as a molecular replacement
search model to solve the complex structure. The E1-E2 heterodimers formed
homotrimers that had the same structure as the trimeric spikes on the virus
surface observed at lower resolution using cryo electron microscopy. The
structure of E2 was found to have three domains (A, B and C) with the A and C
domains forming immunoglobulin-like folds. At the low pH condition used to
grow the crystals, domain B was disordered, which represents an intermediate
state essential for membrane fusion and cell entry.
Figure: Model of the Sindbis virus
capsid. E1 molecules are shown in red, E2 molecules are shown in blue. The
exposed fusion loop of E1 is shown in green.
Citation: Li L, Jose J, Xiang Y, Kuhn RJ, Rossmann MG.
Structural changes of envelope proteins during alphavirus fusion. Nature.
2010 Dec 2; 468: 705-8. doi: 10.1038/nature09546.