Structural biology: An alphavirus puzzle solved

Abstract

Alphaviruses infect their host by binding cellular receptors and fusing with cell membranes. New structures define the receptor-binding protein of these viruses and its regulation of the membrane-fusion reaction.

Figure 1

A. A schematic view of the alphavirus p62/E1 proteins. E1 is shown with domains I, II, and III colored in red, yellow, and blue, respectively, and the fusion loop indicated by the green star. The p62 protein is shown with domain A in cyan, domain B in green, domain C in pink, the ribbon-like connector in purple, the E3 region in grey. The virus membrane is shown in brown. Only 1 p62/E1 pair in the trimeric spike is shown. B. p62 is cleaved by furin, untethering the E3 protein which is released in some alphaviruses. C. Low pH causes the movement of E2 domain B and the connector, exposing the E1 fusion loop. D. E1 inserts into the host cell membrane. E2 releases E1 but the timing of release and the location and conformation of E2 at this stage are undefined. E. E1 forms an extended trimer. F. E1 refolds to a hairpin-like structure via the movement of domain III and the juxtamembrane stem region (grey). This refolding drives membrane fusion. The fused membrane is shown in purple.