Fig. 4: Cryo-EM structures of the NA-antibody complexes.
From: Broad neuraminidase antibodies confer protection against seasonal and avian influenza viruses
A Overall structures of the complexes of NA tetramers and Fabs. Calcium ions (red spheres) and glycans (green) are shown. B Overall structures of Fab-NA protomers. Both CAV-F34 and CAV-F6 Fab utilize HCDR3 to approach into the enzymatic site. C Binding epitopes on the NAs. Footprints of CAV-F34 and CAV-F6 Fabs on the NAs are represented by red surface. The interacted CDRs and FR loops are shown. For all the panels, A/California/04-CIP100_RGCM_1868/2009 (H1N1) NA tetramer, A/Switzerland/9715293/2013 (H3N2) NA tetramer, A/Red knot/Delaware Bay/310/2016 (H10N4) NA tetramer, and A/dairy cow/Minnesota/24_016288-003/2024 (H5N1) NA tetramer are colored by light purple, cyan, cornflower blue and dark violet, respectively. CAV-F34 and CAV-F6 are colored as orange and pink, respectively. Abbreviations: variable domain of heavy chain (VH); variable domain of kappa chain (VK); complementarity-determining region (CDR); framework region (FR). D–H Detailed interactions between the NA enzymatic site and HCDRs. Salt bridges and hydrogen bonds are depicted by solid lines. I–M Detailed interactions between sialic acid (SA) and the NA enzymatic site of A/Tanzania/205/2010 (H3N2) (PDB ID: 4GZQ) (I), A/Tanzania/205/2010 (H3N2) NA and oseltamivir (OSE) (PDB ID: 4GZP) (J), A/Tanzania/205/2010 (H3N2) NA and FNI9 (PDB ID: 4G3N) (K), A/California/04/2009 (H1N1) NA and 1G01 (PDB ID: 6Q23) (L) and A/Kansas/14/2017 (H3N2) NA and 4N2C402 (PDB ID: 8ZR4) (M). Salt bridges and hydrogen bonds are depicted by solid lines, and other interactions within 4 Å are represented by dashed lines. For all the panels, A/Tanzania/205/2010 N2 NA, A/California/04/2009 (H1N1) NA and A/Kansas/14/2017 (H3N2) NA are colored by dark blue, light purple and salmon, respectively. SA, OSE, FNI9, 1G01 and 4N2C402 are colored as yellow, lime, dark green, grey and brown, respectively. N, Sequence logo plot illustrating amino acid conservation of a portion of NA sequences from H1N1 and H5N1 IAVs. O, Sequence logo plot illustrating amino acid conservation of a portion of NA sequences from human seasonal H3N2 IAVs.
