Membrane proteins organize a symmetrical virus

Alphaviruses are enveloped icosahedral viruses that mature by budding at th e plasma membrane. According to a prevailing model maturation is driven by binding of membrane protein spikes to a preformed nucleocapsid (NC). The T = 4 geometry of the membrane is thought to be imposed by the NC through one -to-one interactions between spike protomers and capsid proteins (CPs), Thi s model is challenged here by a Semliki Forest virus capsid gene mutant. It s CPs cannot assemble into NCs, or its intermediate structures, due to defe ctive CP-CP interactions. Nevertheless, it can use its horizontal spike-spi ke interactions on membrane surface and vertical spike-CP interactions to m ake a particle with correct geometry and protein stoichiometry. Thus, our r esults highlight the direct role of membrane proteins in organizing the ico sahedral conformation of alphaviruses.