OmniVira

Structures of Marburgvirus glycoprotein and its complex with NPC1 receptor.

Gang Ye1,2 Fan Bu3,4 Hailey Turner-Hubbard3,4 Morgan Herbst3,4 Lanying Du5 Ge Yang6 Bin Liu7 Fang Li8,9
Affiliations 9 institutions
  1. Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA. [email protected].
  2. Center for Emerging Viruses, University of Minnesota, Minneapolis, MN, USA. [email protected].
  3. Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA.
  4. Center for Emerging Viruses, University of Minnesota, Minneapolis, MN, USA.
  5. Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
  6. Hormel Institute, University of Minnesota, Austin, MN, USA.
  7. Hormel Institute, University of Minnesota, Austin, MN, USA. [email protected].
  8. Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA. [email protected].
  9. Center for Emerging Viruses, University of Minnesota, Minneapolis, MN, USA. [email protected].
PMID41813895 DOI10.1038/s41586-026-10240-0 Year2026 Journal Nature Languageeng Statusaheadofprint

Abstract

Marburgviruses (MBVs) cause severe haemorrhagic fever with higher fatality rates than Ebola virus (EBOV)1-4. Here we show that the MBV glycoprotein (GP) mediates viral entry more efficiently than EBOV GP. Using cryo-EM, we determined structures of MBV GP in three states: (1) unbound; (2) bound to its endosomal receptor NPC1; and (3) complexed with a neutralizing nanobody. The glycan cap shields the receptor-binding site from NPC1 but only partially from the nanobody, enabling limited immune evasion. After glycan cap cleavage, NPC1 binds to MBV GP in a distinct orientation compared with EBOV GP, providing an additional anchor and enhancing receptor affinity. NPC1 engagement also induces substantial conformational changes in MBV GP, probably facilitating membrane fusion. Furthermore, MBV GP is susceptible to the neutralizing nanobody, which mimics NPC1 at the receptor-binding site. Together, our findings reveal MBV GP as a highly efficient entry mediator and suggest structural mechanisms that may contribute to its enhanced entry efficiency.

Supporting text Virus Host Location

Evidence records

1 total
Functional Mechanism
1 records · 1 evidence types
Evidence type Receptor Usage
1 records
OVE10669 Receptor Usage
Key finding

Cryo-EM structures demonstrate that Marburgvirus glycoprotein directly binds the endosomal receptor NPC1 in a distinct orientation compared with Ebola virus glycoprotein, enhancing receptor affinity.

Virus
Marburg virus Ebola virus
Host
Not specified
Location
Not specified
Supporting text

After glycan cap cleavage, NPC1 binds to MBV GP in a distinct orientation compared with EBOV GP, providing an additional anchor and enhancing receptor affinity.

Method
cryo-EM structural analysis
Receptors
NPC1