Both heptad repeats of human respiratory syncytial virus fusion protein are potent inhibitors of viral fusion.
Heptad repeat regions (HR1 and HR2) are highly conserved peptides located in F(1) of paramyxovirus envelope proteins. They are important in the process of virus fusion and form six-helix bundle structure (trimer of HR1 and HR2 heterodimer) post-fusion, similar to those found in the fusion proteins of other enveloped viruses, such as retrovirus HIV. Both HR1 and HR2 show potent inhibition for virus fusion in some members of paramyxovirus. However, in other members, only HR2 gives strong inhibition whereas HR1 does not. Human respiratory syncytial virus (hRSV) is a member of paramyxovirus and its crystal structure of HR1 and HR2 six-helix bundle was solved lately. Although hRSV HR2 inhibition was reported, nevertheless the effect of HR1 on virus fusion is not known. In this study, hRSV HR1 and HR2 were expressed as fusion protein separately in Escherichia coli system and their complex assembly and virus fusion inhibition effect have been analysed. It shows that both HR1 and HR2 (in the fusion form with 50-amino-acid fusion partner) of hRSV F protein give strong inhibition on virus fusion (IC(50) values are 1.68 and 2.93 microM, respectively) and they form stable six-helix bundle in vitro with both in the fusion protein form.
Wang
Enxiu
E
Department of Molecular Virology and Bio-Engineering, Institute of Microbiology, Chinese Academy of Sciences, Zhongguancun Beiyitiao, Beijing 100080, China.
Sun
Xiao'ou
X
Qian
Yuan
Y
Zhao
Linqing
L
Tien
Po
P
Gao
George F
GF
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002850:Chromatography, Gel; D002942:Circular Dichroism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000494:pharmacology*; D018113:Respiratory Syncytial Virus, Human / Q000378:metabolism*; D018108:Respirovirus / Q000378:metabolism
D000998:Antiviral Agents; D003432:Cross-Linking Reagents; D011993:Recombinant Fusion Proteins