LOW PH INDUCES SWIVELING OF THE GLYCOPROTEIN HETERODIMERS IN THE SEMLIKI-FOREST VIRUS SPIKE COMPLEX

Time-resolved cryoelectron microscopy reveals the first step in the co nformational changes that enable membrane fusion in Semliki Forest vir us. The neutral pH structure reveals a central cavity within the spike complex, plate-like extensions forming a layer above the membrane, an d the paths of the paired transmembrane domains connecting the trimeri c spikes and pentamer-hexamer clustered capsid subunits. Low pH treatm ent results in centrifugal movement of E2, the receptor-binding subuni t, centripetal movement of E1 to narrow the central cavity initiating the formation of an E1 trimer, and the extension of the E1 fusion sequ ence toward the target membrane.