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.



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