Characterization of HCoV-229E fusion core: implications for structure basis of coronavirus membrane fusion.
Human coronavirus 229E (HCoV-229E), a member of group I coronaviruses, has been identified as one of the major viral agents causing respiratory tract diseases in humans for nearly 40 years. However, the detailed molecular mechanism of the membrane fusion mediated by the spike (S) protein of HCoV-229E remains elusive. Here, we report, for the first time, a rationally designed fusion core of HCoV-229E (HR1-SGGRGG-HR2), which was in vitro produced in GST prokaryotic expression system. Multiple lines of experimental data including gel-filtration, chemical cross-linking, and circular diagram (CD) demonstrated that the HCoV-229E fusion core possesses the typical properties of the trimer of coiled-coil heterodimer (six alpha-helix bundle). 3D structure modeling presents its most-likely structure, similar to those of coronaviruses that have been well-documented. Collectively, HCoV-229E S protein belongs to the type I fusion protein, which is characterized by the existence of two heptad-repeat regions (HR1 and HR2), furthermore, the available knowledge concerning HCoV-229E fusion core may make it possible to design small molecule or polypeptide drugs targeting the membrane fusion, a crucial step of HCoV-229E infection.
Liu
Cheng
C
College of Veterinary Medicine, China Agricultural University, Beijing 100094, PR China.
Feng
Youjun
Y
Gao
Feng
F
Zhang
Qiangmin
Q
Wang
Ming
M
D000595:Amino Acid Sequence; D028941:Coronavirus 229E, Human / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D019281:Dimerization; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014758:Viral Core Proteins / Q000737:chemistry*; D014760:Viral Fusion Proteins / Q000378:metabolism*
D003432:Cross-Linking Reagents; D011993:Recombinant Fusion Proteins; D014758:Viral Core Proteins; D014760:Viral Fusion Proteins; D005982:Glutathione Transferase