Alphaviruses are enveloped RNA viruses that use arthropods such as mosquitoes for transmission to their vertebrate hosts, and include Semliki Forest and Sindbis viruses PMID:15378043. Alphaviruses consist of three structural proteins: the core nucleocapsid protein C, and the envelope proteins P62 and E1 which associate as an heterodimer. The viral membrane-anchored surface glycoproteins are responsible for receptor recognition and entry into target cells through membrane fusion. P62 maturates through proteolysis into E2 and E3, process which causes a change in the viral surface. Association between E1, E2 and sometimes E3 glycoprotein "spikes" result in formation of a E1/E2 dimer or an E1/E2/E3 trimer, where E2 extends from the centre to the vertices, E1 fills the space between the vertices, and E3, if present, is at the distal end of the spike PMID:8107141,PMID:9445057. Exposure of the virus to the low pH of the endosome results in dissociation of E1 from E2 and subsequent formation of an E1 homotrimer, necessary for the fusion of cellular and viral membranes PMID:11301009.

The E2 glycoproteins interact with the nucleocapsid through its cytoplasmic domain, while its ectodomain is responsible for binding a cellular receptor. This is an all beta protein belonging to the immunoglobulin superfamily, with three immunoglobulin domains labelled A, B and C in amino- to carboxy-terminal order PMID:21124458. Structural domains comprising this superfamily share the structure of the C-terminal domain, known as domain C, of the alphavirus E2 glycoprotein.