1.G.2 The Viral Pore-forming Membrance Fusion Protein-2 (VMFP2) Family

Like the Influenza HA protein, the Paramyxovirus F protein is of Class I (White et al. 2008) and shares the characteristics noted in the description for family 1.H.1. It is the second best charaterized Class I viral fusion protein. The crystal structures of various ectodomains are known. The F protein consists of three domains, domains, I, II, and III (Lamb and Jardetzky, 2007).

This family belongs to the Viral Envelope Fusion Protein (Env-FP) Superfamily.



Apellaniz B., Huarte N., Largo E. and Nieva JL. (2014). The three lives of viral fusion peptides. Chem Phys Lipids. 181:40-55.

Cifuentes-Muñoz, N., W. Sun, G. Ray, P.T. Schmitt, S. Webb, K. Gibson, R.E. Dutch, and A.P. Schmitt. (2017). Mutations in the Transmembrane Domain and Cytoplasmic Tail of Hendra Virus Fusion Protein Disrupt Virus-Like-Particle Assembly. J. Virol. 91:.

Lamb, R.A. and T.S. Jardetzky. (2007). Structural basis of viral invasion: lessons from paramyxovirus F. Curr. Opin. Struct. Biol. 17: 427-436.

Li Z., Hung C., Paterson RG., Michel F., Fuentes S., Place R., Lin Y., Hogan RJ., Lamb RA. and He B. (2015). Type II integral membrane protein, TM of J paramyxovirus promotes cell-to-cell fusion. Proc Natl Acad Sci U S A. 112(40):12504-9.

McLellan, J.S., M. Chen, S. Leung, K.W. Graepel, X. Du, Y. Yang, T. Zhou, U. Baxa, E. Yasuda, T. Beaumont, A. Kumar, K. Modjarrad, Z. Zheng, M. Zhao, N. Xia, P.D. Kwong, and B.S. Graham. (2013). Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science 340: 1113-1117.

White, J.M., S.E. Delos, M. Brecher, and K. Schornberg. (2008). Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme. Crit. Rev. Biochem. Mol. Biol. 43: 189-219.

Yao, H., M. Lee, S.Y. Liao, and M. Hong. (2016). Solid-State NMR Investigation of the Structural Topology and Lipid Interactions of a Viral Fusion Protein Chimera Containing the Fusion Peptide and Transmembrane Domain. Biochemistry. [Epub: Ahead of Print]


TC#NameOrganismal TypeExample
1.G.2.1.1The Paramyxovirus (Class I) fusion (F) protein (545 aas)VirusProtein F of Paramyxovirus (Q5S8E4)

Fusion glycoprotein FO (Class I) (565 aas) (31% identical throughout its length with 1.H.2.1.1) (Lamb and Jardetzky 2007).  Interacts with protein G and protein TM in J paramyxovirus to promote fusion (Li et al. 2015).


The paramyxovirus F fusion protein of Sendai virus (P04855)


The respiratory syncytial virus (RSV) fusion (F) glycoprotein.  The crystal strcuture is available (McLellan et al. 2013).  The protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and plasma cell membranes which leads to delivery of the nucleocapsid into the cytoplasm. Fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (protein F) interacts with glycoprotein G at the virion surface. Upon binding of G to heparan sulfate, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between host cell and virion membranes. RSV fusion protein is able to interact directly with heparan sulfate and therefore actively participates in virus attachment.


F-glycoprotein of respiatory syncytial virus


The fusion glycoprotein F0 of 94 aas


F0 of Newcastle Disease Virus


Fusion glycoprotein F0 of 550 aas


Fusion glycoprotein of Measles virus


Fusion glycoprotein of 529 aas (Apellániz et al. 2014). Loosely associated fusion peptide and TMS helices generate significant negative Gaussian curvature to membranes that possess spontaneous positive curvature, consistent with fusion peptide-TMS assembly facilitating the transition of the membrane from hemifusion intermediates to the fusion pore (Yao et al. 2016).

Viruses (Orthomyxoviridae)

Fusion protein of influenza virus 5 (PIV5)


Fusion glycoprotein F0 of 546 aas and 2 TMSs (N- and C-terminal) (Apellániz et al. 2014). The unique endocytic trafficking pathway of Hendra virus F protein is required for proper viral assembly and particle release (Cifuentes-Muñoz et al. 2017).

Viruses (Paramyxoviridae)

F0 of Hendra virus