9B8G

2C9 Fab antibody fragment against the E protein of the Yellow Fever virus

Summary for 9B8G

• Entry DOI: 10.2210/pdb9b8g/pdb
• Descriptor: 2C9 Fab heavy chain, 2C9 Fab light chain, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: antibody, fab, flavivirus, yellow fever, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 146851.36

Authors

Balk, J.,Ting, Y.T.,Bibby, S.,Watterson, D.,Coulibaly, F. (deposition date: 2024-03-29, release date: 2024-11-06, Last modification date: 2025-10-15)

Primary citation

Bibby, S.,Jung, J.,Low, Y.S.,Amarilla, A.A.,Newton, N.D.,Scott, C.A.P.,Balk, J.,Ting, Y.T.,Freney, M.E.,Liang, B.,Grant, T.,Coulibaly, F.,Young, P.,Hall, R.A.,Hobson-Peters, J.,Modhiran, N.,Watterson, D.
A single residue in the yellow fever virus envelope protein modulates virion architecture and antigenicity.
Nat Commun, 16:8449-8449, 2025

PubMed Abstract: Yellow fever virus (YFV) is a re-emerging flavivirus that causes severe hepatic disease and mortality in humans. Despite being researched for over a century, the structure of YFV has remained elusive. Here we use a chimeric virus platform to resolve the first high resolution cryo-EM structures of YFV. Stark differences in particle morphology and homogeneity are observed between vaccine and virulent strains of YFV, and these are found to have significant implications on antibody recognition and neutralisation. We identify a single residue (R380) in the YFV envelope protein that stabilises the virion surface, and leads to reduced exposure of the cross-reactive fusion loop epitope. The differences in virion morphology between YFV strains also contribute to the reduced sensitivity of the virulent YFV virions to vaccine-induced antibodies. These findings have significant implications for YFV biology, vaccinology and structure-based flavivirus antigen design.

PubMed: 41006244
DOI: 10.1038/s41467-025-63038-5

Experimental method

X-RAY DIFFRACTION (2.66 Å)