Two disulfide-linked polypeptide chains constitute the active F protein of paramyxoviruses.

The paramyxovirus glycoprotein which is required for virus-induced cell fusion, hemolysis, and the initiation of infection (F protein) has been found with three different viruses to consist of two disulfide-linked glycopolypeptide chains (F₁ and F₂) which are derived from the precursor glycopolypeptide (F₀) by proteolytic cleavage. The larger glycopolypeptide chain (F₁) previously identified in SV5, Sendai, and Newcastle disease virions has an estimated molecular weight of 48,000–54,000. The smaller polypeptide chain (F₂) has been found to have a molecular weight of ～10,000–16,000, depending on the virus. The identification of the F₂ polypeptide was accomplished by isolating the disulfide-linked complex (F_1,2) under nonreducing conditions, followed by reduction of the disulfide bonds and separation of the two polypeptide chains. Although both polypeptides are glycosylated, the F₂ polypeptide contains more carbohydrate per unit protein than F₁. No free N-terminus could be detected on the F₀ or F₂ polypeptides of Sendai virus, whereas N-terminal phenylalanine was found on F₁. This suggests that the order of the F₀ polypeptide is X-NH-F₂—Phe-F₁—COOH. The finding that with three different paramyxoviruses the biologically active virions possess F₁ and F₂ polypeptides suggests that this is a general feature of paramyxoviruses, and that the activation of infectivity, cell fusion, and hemolysis is due to a conformational change in the F protein resulting from proteolytic cleavage to form an active complex of two disulfide-linked polypeptide chains.