7A56

Schmallenberg Virus Envelope Glycoprotein Gc Fusion Domains in Postfusion Conformation

Summary for 7A56

• Entry DOI: 10.2210/pdb7a56/pdb
• Descriptor: Envelopment polyprotein, CHLORIDE ION, PHOSPHATE ION, ... (6 entities in total)
• Functional Keywords: virus entry, class ii membrane fusion protein, viral protein
• Biological source: Bovine Schmallenberg virus BH80/Germany/2011
• Total number of polymer chains: 1
• Total formula weight: 48928.67

Authors

Hellert, J.,Guardado-Calvo, P.,Rey, F.A. (deposition date: 2020-08-20, release date: 2021-09-01, Last modification date: 2024-10-16)

Primary citation

Hellert, J.,Aebischer, A.,Haouz, A.,Guardado-Calvo, P.,Reiche, S.,Beer, M.,Rey, F.A.
Structure, function, and evolution of the Orthobunyavirus membrane fusion glycoprotein.
Cell Rep, 42:112142-112142, 2023

PubMed Abstract: La Crosse virus, responsible for pediatric encephalitis in the United States, and Schmallenberg virus, a highly teratogenic veterinary virus in Europe, belong to the large Orthobunyavirus genus of zoonotic arthropod-borne pathogens distributed worldwide. Viruses in this under-studied genus cause CNS infections or fever with debilitating arthralgia/myalgia syndromes, with no effective treatment. The main surface antigen, glycoprotein Gc (∼1,000 residues), has a variable N-terminal half (Gc) targeted by the patients' antibody response and a conserved C-terminal moiety (Gc) responsible for membrane fusion during cell entry. Here, we report the X-ray structure of post-fusion La Crosse and Schmallenberg virus Gc, revealing the molecular determinants for hairpin formation and trimerization required to drive membrane fusion. We further experimentally confirm the role of residues in the fusion loops and in a vestigial endoplasmic reticulum (ER) translocation sequence at the Gc-Gc junction. The resulting knowledge provides essential molecular underpinnings for future development of potential therapeutic treatments and vaccines.

PubMed: 36827185
DOI: 10.1016/j.celrep.2023.112142

Experimental method

X-RAY DIFFRACTION (1.85 Å)