The subfamily Paramyxovirinae of the family Paramyxoviridae contains three genera, Respirovirus, Rubulavirus, and Morbillivirus (9, 31, 40). Two kinds of glycoproteins, hemagglutinin-neuraminidase (HN) and fusion (F) protein, are inserted in the viral envelope of the members of the genera Respirovirus and Rubulavirus. The HN protein is responsible for binding to sialic acid-containing cellular molecules and for enzymatic cleavage of the sialoconjugate, while the F protein is involved in envelope-to-cell and cell-to-cell fusion (cell fusion) (9, 31).The F protein is activated from a precursor (F0) when cleaved by cellular protease(s) and forms a disulfide-bonded subunit structure consisting of F1 and F2, which is a prerequisite for the fusion process (22,42). The well-conserved hydrophobic domain (fusion peptide) at the amino terminus of F1 is exposed by the cleavage (25,29) and is considered likely to be directly involved in the fusion event (17, 37). The cleavage also results in a conformational change of the F protein (13,25,29,54). Three heptad repeat (HR) domains are found in the F1 ectodomain (6, 18). The HR1 domain is immediately next to the carboxyl terminus of the fusion peptide, while the HR2 domain is close to the transmembrane domain. The HR3 domain is located between the FR1 and HR2 domains (18) and is followed by a highly conserved stretch of eight cysteine residues (the cysteine-rich domain) (6). Crystallographic analyses have shown that polypeptide fragments representing the