heptad repeat 1- heptad repeat 2 region (ectodomain) of the transmembrane subunit of the human endogenous retrovirus HERV-R(b)_c3p24.3 and related domains
This domain subfamily spans both heptad repeats of the glycoprotein (gp)/transmembrane subunit of various endogenous retroviruses (ERVs) including the human ERVs (HERVs): HERV-R(b)_c3p24.3 and Syncytin-3 (also known as HERV-P(b)_c14q32.12). This domain belongs to a larger superfamily containing the HR1-HR2 domain of endogenous retroviruses (ERVs) and infectious retroviruses, such as Ebola virus, Rous sarcoma virus (RSV) and human immunodeficiency virus type 1 (HIV-1). This domain includes an N-terminal heptad repeat, a CKS17-like immunosuppressive region, a CX6C motif that forms an intrasubunit disulfide bond, and a C-terminal, is a heptad repeat. In intact retroviruses, N-terminal to HR1-HR2 region is a fusion peptide (FP), and C-terminal, is a membrane-spanning region (MSR). Viral infection involves the formation of a trimer-of-hairpins structure (three HR1s helices, buttressed by three HR2 helices lying in antiparallel orientation). In this structure, the FP (inserted in the host cell membrane) and MSR (inserted in the viral membrane) are in close proximity. ERVs are likely to originate from ancient germ-line infections by active retroviruses. Some ERVs play specific roles in the host, including placental development, protection of the host from infection by related pathogenic and exogenous retroviruses, and genome plasticity. Syncytin-3 is fusogenic, HERV-R(b)_c3p24.3 appears not to have fusogenic activity.
Comment: The conformation of Ebola virus HR1 changes significantly in the pre-fusion (three-helix bundle) and post-fusion (six-helix bundle) conformations of the HR1-HR2 region.
Jiyao W et al.(2023). "The conserved domain database in 2023.",