9PFK

Cryo-EM structure of VX93 Fab in complex with GII.4 Norovirus P domain

Summary for 9PFK

• Entry DOI: 10.2210/pdb9pfk/pdb
• EMDB information: 71603
• Descriptor: VP1, VX93 heavy chain, VX93 light chain (3 entities in total)
• Functional Keywords: norovirus, antibody complex, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Norovirus Hu/GII.4/Sydney/NSW0514/2012/AU; More
• Total number of polymer chains: 6
• Total formula weight: 121783.54

Authors

Jo, G.,Ward, A.B. (deposition date: 2025-07-04, release date: 2026-07-01, Last modification date: 2026-09-02)

Primary citation

Park, J.,Jo, G.,Reyes, Y.,Pickens, W.,Kim, D.S.,Beaver, A.,Costantini, V.P.,Liu, C.,Kim, D.,Park, D.,Longo, V.,Brewer-Jensen, P.D.,Mallory, M.L.,Satterwhite, E.,Zapata-Bustos, R.,Marchioni, J.,Zweigart, M.R.,Flitter, B.A.,Vinje, J.,Han, J.,Ross, T.M.,Lee, J.,Lavinder, J.J.,Tucker, S.N.,Ke, Z.,Ward, A.B.,Lindesmith, L.C.,Baric, R.S.,Georgiou, G.
Serum IgA proteomics reveals clonal composition and neutralization of dimeric and monomeric IgA repertoires against human norovirus.
Proc.Natl.Acad.Sci.USA, 123:e2603905123-e2603905123, 2026

PubMed Abstract: Protection against human norovirus correlates with attachment ligand blockade antibody titers, fecal IgA titers, and serum IgA titers. IgA responses in serum comprise approximately 80 to 95% of monomeric IgA (mIgA) and 5 to 20% of dimeric IgA (dIgA). Using serum LC-MS/MS proteomics, we established clonal relationships between circulating IgG and IgA, as well as between dIgA and mIgA. We observed a modest degree of clonal overlap between circulating IgG and IgA at steady state and found that more than 80% of antigen-specific mIgA was also detectable as dIgA. We biochemically characterized neutralizing epitopes on norovirus GII.4 virus-like particles (VLPs) targeted by serum IgA clonotypes and demonstrated that dIgA markedly enhances neutralization potency relative to mIgA and IgG in an epitope-specific manner. Cryoelectron microscopy and cryoelectron tomography revealed that whether IgA dimerization enhances viral neutralization depends on epitope accessibility on the VLP and antibody binding orientation. Together, these findings provide molecular-level resolution of the serum IgA response and define the structural basis by which dIgA enhances neutralization potency in an epitope-specific manner.

PubMed: 42607213
DOI: 10.1073/pnas.2603905123

Experimental method

ELECTRON MICROSCOPY (2.93 Å)