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Table 1.

Amino-acid composition in the receptor-binding site of H6 HA proteins.

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Table 1 Expand

Table 2.

Binding kinetics of H6 HAs with avian and human receptor analogues.

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Table 2 Expand

Fig 1.

The overall structures of GD and TW H6 HAs.

a). One monomer of GD H6 HA (in yellow color) with the glycans (in stick model). The receptor-binding site (RBS) is labeled. b). One monomer of TW H6 HA (in blue color) with the glycans (in stick model). c). Superposition of the monomers of GD (in yellow color) and TW (in blue color) H6 HAs. d). Comparison of the receptor-binding sites of GD (in yellow) and TW (in blue) H6 HAs. Highlighted are the residues at or surrounding the receptor-binding site. All residues are in H3 HA numbering. e). Comparison of the receptor-binding sites of GD (in yellow) and TW (in blue) H6 HAs with H1 HA from A/Brevig Mission/1/1918(H1N1) (PDB code: 2WRG; in magenta), H2 HA from A/Singapore/1/1957(H2N2) (PDB code: 2WR7; in orange), H3 HA from A/Aichi/2/68(H3N2) (PDB code: 2YPG; in green), H5 HA from an airborne transmissible mutant of A/Indonesia/5/2005(H5N1) (PDB code: 4K67; in cyan), H7 HA from A/Anhui/1/2013(H7N9) (PDB code: 4BSB; in purple), H9 HA from A/swine/Hong Kong/9/1998(H9N2) (PDB code: 1JSI; in grey), H10 HA from A/Jiangxi/Donghu/346/2013(H10N8) (PDB code: 4QY2; in forest), and H13 HA from A/gull/Maryland/704/1977(H13N6) (PDB code: 4KPS; in pink). The strictly conserved residues among all these HAs within the receptor-binding sites, Y98, W153, H183 and Y195, are shown. Also shown are the main chains of HA1 133 that display different configurations among these structures.

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Fig 1 Expand

Fig 2.

Structural comparison of H6 HAs in binding to avian receptor analogues.

a). GD H6 HA-LSTa complex. GD H6 HA structure is shown in yellow and LSTa is in green. The composite omit 2Fo-Fc electron density map for the receptor is shown at 1σ. The hydrogen bonds detected by LIGPLOT are shown as black dashed lines. b). TW H6 HA-LSTa complex. TW H6 HA structure is shown in blue and LSTa is in green. The composite omit 2Fo-Fc electron density map for the receptor is shown at 1σ. The hydrogen bonds detected by LIGPLOT are shown as black dashed lines. c). Comparison of LSTa interaction with GD (in yellow) and TW (in blue) H6 HAs. The hydrogen bonds different between these two complexes are shown as dashed lines (yellow dashed lines for hydrogen bonds unique to GD H6 HA-LSTa; blue dashed lines for hydrogen bonds unique to TW H6 HA-LSTa). Highlighted by arrows are the different sitting positions of the LSTa Sia-1 moiety in the receptor-binding sites of GD and TW H6 HAs. d). Comparison of avian receptor analogues in GD H6 HA (in yellow) with avian H1 HA from A/WDK/JX/12416/2005(H1N1) (PDB code: 3HTP; in green). e). Comparison of avian receptor analogues in GD H6 HA (in yellow) with avian H5 HA from A/Indonesia/5/2005(H5N1) (PDB code: 4K63; in grey). f). Comparison of avian receptor analogues in TW H6 HA (in blue) and H5 HA from an airborne transmissible mutant of A/Indonesia/5/2005(H5N1) (PDB codes: 4K66; in red). g). Comparison of avian receptor analogues in TW H6 HA (in blue) and H5 HA from a transmissible mutant of A/Vietnam/1203/2004(H5N1) (PDB code: 4BH4; in cyan).

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Fig 2 Expand

Table 3.

Hydrogen bonds between H6 HA proteins and bound receptors.

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Table 3 Expand

Fig 3.

Structural comparison of H6 HAs in binding to human receptor analogues.

a). GD H6 HA-LSTc complex. GD H6 HA structure is shown in yellow and LSTc is in green. The composite omit 2Fo-Fc electron density map for the receptor is shown at 1σ. The hydrogen bonds detected by LIGPLOT are shown as black dashed lines. b). TW H6 HA-LSTc complex. TW H6 HA structure is shown in blue and LSTc is in green. The composite omit 2Fo-Fc electron density map for the receptor is shown at 1σ. The hydrogen bonds detected by LIGPLOT are shown as black dashed lines. c). Comparison of LSTc interaction with GD (in yellow) and TW (in blue) H6 HAs. The hydrogen bonds different between these two complexes are shown as dashed lines (yellow dashed lines for hydrogen bonds unique to GD H6 HA-LSTc; blue dashed lines for hydrogen bonds unique to TW H6 HA-LSTc). The arrow is to highlight the different sitting positions of the LSTc Sia-1 moiety in the receptor-binding sites of GD and TW H6 HAs. d). Comparison of human receptor analogues in TW H6 HA (in blue) and H2 HA from the pandemic A/Singapore/1/1957(H2N2) virus (PDB code: 2WR7; in green). e). Comparison of human receptor analogues in TW H6 HA (in blue) and H3 HA from the pandemic A/Aichi/2/68(H3N2) virus (PDB code: 2YPG; in grey). f). Comparison of human receptor analogues in TW H6 HA (in blue) and H5 HA from a transmissible mutant of A/Vietnam/1203/2004(H5N1) (PDB code: 4BH3; in red).

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Fig 3 Expand