The structure of a complex between the NC10 antibody and influenza virus neuraminidase and comparison with the overlapping binding site of the NC41 antibody

Abstract

The capacity of two different proteins to bind to the same target structure on a third protein need not be based on the existence of identical or homologous amino acid sequences within those proteins. As we have demonstrated, amino acid residues on the common target structure may be in quite different chemical environments, and may also adopt different conformations within two protein-protein complexes.

Structural Characterization of the 1918 Influenza Virus H1N1 Neuraminidase

“…2). The 330 loop, restrained by a disulfide bridge via Cys336, has been previously identified as one of the antigenic sites and contributes to the binding of two antibodies, NC41 and NC10, as shown by analysis using escape mutants and crystal structures (1,28,46). NA sequences from both group 1 and group 2 show insertions and deletions in this region.…”

Antibody Epitopes on the Neuraminidase of a Recent H3N2 Influenza Virus (A/Memphis/31/98)

“…We then searched with just the Fv domain from 1NCA and located it (correlation coefficient, 59.3%; R factor, 35.0%). Finally, we searched separately for the C domain of the Fab, but it was not located by AMORE, suggesting that the elbow angle is mobile, as it was in the N9NA-NC10 complex crystal structure (25), or that the packing is not well ordered. A refinement of the structure and inclusion of side chains of Mem98 NA complexed with Fv of antibody Mem5 await better-quality crystals, but the 3.5-Å molecular replacement structure shows the Fv domain sitting over the sites of escape mutations (see Fig.…”

“…We have even more detailed views of epitopes on N9 NA (3,20,27,28,40) since crystal structures of antibody Fab fragments bound to N9 NA have been obtained (25,37,38). Many years ago, Laver crystallized N2 NAs from viruses isolated between 1957 and 1967, but NAs of viruses isolated after about 1975 did not crystallize (16,18).…”

Influenza virus neuraminidase: Structure, antibodies, and inhibitors

“…5 ; Colman et al, 1987;Tulip et al, 1992a;Malby et al, 1994). Both illustrate the importance of large and complementary buried surfaces in the formation of complexes between protein antigen and antibody.…”