EMD-29300
Mojiang virus F ectodomain in prefusion form
EMD-29300
Single-particle2.66 Å
Deposition: 26/12/2022Map released: 28/06/2023
Last modified: 20/11/2024
Sample Organism:
Mojiang virus
Sample: Mojiang virus F glycoprotein ectodomain in the prefusion form
Fitted models: 8fmy (Avg. Q-score: 0.564)
Deposition Authors: Low YS, Isaacs A
,
Modhiran N ,
Watterson D
Sample: Mojiang virus F glycoprotein ectodomain in the prefusion form
Fitted models: 8fmy (Avg. Q-score: 0.564)
Deposition Authors: Low YS, Isaacs A
,
Modhiran N ,
Watterson D
Structure and antigenicity of divergent Henipavirus fusion glycoproteins.
Isaacs A ,
Low YS,
Macauslane KL ,
Seitanidou J ,
Pegg CL ,
Cheung STM,
Liang B ,
Scott CAP,
Landsberg MJ ,
Schulz BL ,
Chappell KJ ,
Modhiran N ,
Watterson D
(2023) Nat Commun , 14 , 3577 - 3577
,
Low YS,
Macauslane KL ,
Seitanidou J ,
Pegg CL ,
Cheung STM,
Liang B ,
Scott CAP,
Landsberg MJ ,
Schulz BL ,
Chappell KJ ,
Modhiran N ,
Watterson D
(2023) Nat Commun , 14 , 3577 - 3577
Abstract:
In August 2022, a novel henipavirus (HNV) named Langya virus (LayV) was isolated from patients with severe pneumonic disease in China. This virus is closely related to Mòjiāng virus (MojV), and both are divergent from the bat-borne HNV members, Nipah (NiV) and Hendra (HeV) viruses. The spillover of LayV is the first instance of a HNV zoonosis to humans outside of NiV and HeV, highlighting the continuing threat this genus poses to human health. In this work, we determine the prefusion structures of MojV and LayV F proteins via cryogenic electron microscopy to 2.66 and 3.37 Å, respectively. We show that despite sequence divergence from NiV, the F proteins adopt an overall similar structure but are antigenically distinct as they do not react to known antibodies or sera. Glycoproteomic analysis revealed that while LayV F is less glycosylated than NiV F, it contains a glycan that shields a site of vulnerability previously identified for NiV. These findings explain the distinct antigenic profile of LayV and MojV F, despite the extent to which they are otherwise structurally similar to NiV. Our results carry implications for broad-spectrum HNV vaccines and therapeutics, and indicate an antigenic, yet not structural, divergence from prototypical HNVs.
In August 2022, a novel henipavirus (HNV) named Langya virus (LayV) was isolated from patients with severe pneumonic disease in China. This virus is closely related to Mòjiāng virus (MojV), and both are divergent from the bat-borne HNV members, Nipah (NiV) and Hendra (HeV) viruses. The spillover of LayV is the first instance of a HNV zoonosis to humans outside of NiV and HeV, highlighting the continuing threat this genus poses to human health. In this work, we determine the prefusion structures of MojV and LayV F proteins via cryogenic electron microscopy to 2.66 and 3.37 Å, respectively. We show that despite sequence divergence from NiV, the F proteins adopt an overall similar structure but are antigenically distinct as they do not react to known antibodies or sera. Glycoproteomic analysis revealed that while LayV F is less glycosylated than NiV F, it contains a glycan that shields a site of vulnerability previously identified for NiV. These findings explain the distinct antigenic profile of LayV and MojV F, despite the extent to which they are otherwise structurally similar to NiV. Our results carry implications for broad-spectrum HNV vaccines and therapeutics, and indicate an antigenic, yet not structural, divergence from prototypical HNVs.