by Thomas Bowden, Division of Structural Biology, University of Oxford (with some input from Oliver Pybus). Email:

(A) The homotrimeric structure of the mature H7 hemagglutinin (PDB ID 1TI8; A/turkey/Italy/220158/2002-H7N3) [1] is shown in cartoon representation with carbohydrate residues observed in the crystal structure displayed as yellow sticks.

(B) View of panel A rotated by 90 degrees from that in panel A.  The Shanghai and Turkey strains share very high sequence identity (96%). Given the relationship between sequence and structure established by Chothia and Lesk [2], this would suggest at most a 0.6-Å root-mean-square-deviation between structures.  For viewing purposes, two of the three protomers in the homotrimer are obscured with high transparency.  The four amino acids that occurred in the ancestral lineage of the H9N7 outbreak (I211, I188, D183, and N455; full details here) are mapped onto the 1TI8 structure and shown as green spheres.  Three of these residues are located in the HA1 subunit and one is located in HA2.  Residues in the HA1 subunit are unlikely to have an effect upon receptor-binding as they are distant from the HA1 receptor-binding face. Residues which are likely to be involved in receptor-binding are displayed as red spheres.  I211, the nearest residue, is located over 8-Å from the nearest receptor-binding residue, H192.  N455, which is located on HA2, on the other hand, is located closely to the fusion peptide (4.0-Å).  However, it is unlikely that the effect of the D455N substitution is functionally significant, as both residues are charged.  Note, this residue is a serine in North American H7N2 influenza [3]. Finally, three out of the four substituted amino acids are not solvent accessible.  This is suggestive of a limited change in antigenicity. 

(C) Structure-based sequence alignment of the influenza HA7 glycoprotein.  Residues highlighted in red (in white text) are fully conserved, residues in red text are partially conserved, and residues in black text are not conserved.  Residues that are solvent accessible (as determined by ESPRIPT [4]) are annotated below the sequence; light blue is partially accessible, dark blue is fully accessible.  Secondary structure elements were generated from the mature H7 hemagglutinin (PDB ID 1TI8 [1]) and are shown above the sequence: spiral = α-helix, arrows = β-strand.  The green numbering below the alignment marks the disulfide bond pairs.  Regions of the sequence underlined with a yellow bar correspond to amino acids predicted to have N-linked glycosylation, red bars are predicted to be involved in receptor binding [3], green bars  indicate the abovementioned ancestral changes (D183, I188, I211, and N455), grey bars indicate HA0 cleavage site, and black bars indicate the putative fusion peptide [5].



[1] Russell, R. J. et al. H1 and H7 influenza haemagglutinin structures extend a structural classification of haemagglutinin subtypes. Virology 325, 287-296 (2004).

[2] Chothia, C. & Lesk, A. M. The relation between the divergence of sequence and structure in proteins. EMBO J. 5, 823-826 (1986).

[3] Yang, H., Chen, L. M., Carney, P. J., Donis, R. O. & Stevens, J. Structures of receptor complexes of a North American H7N2 influenza hemagglutinin with a loop deletion in the receptor binding site. PLoS Pathog 6, e1001081 (2010).

[4] Gouet, P., Courcelle, E., Stuart, D. I. & Metoz, F. ESPript: analysis of multiple sequence alignments in PostScript. Bioinformatics 15, 305-308 (1999).

[5] Cross, K. J., Langley, W. A., Russell, R. J., Skehel, J. J. & Steinhauer, D. A. Composition and functions of the influenza fusion peptide. Protein and Peptide Letters 16, 766-778 (2009).