Receptor Binding Properties of Neuraminidase for influenza A virus: An Overview of Recent Research Advances

Figures & data

Figure 1. (a) the structure of the NA protein tetrad displaying the head region is depicted. Each monomer is shown to have an SA residue attached to its head, which serves as the site of enzyme activity. (b) the four polypeptide monomers of NA fold and assemble into a tetrameric structure encompassing a spherical head region, a stem, a transmembrane region, and a cytoplasmic tail. The head region of the depicted NA was derived from the Protein Data Bank (PDB:4GZW), and the corresponding protein model was generated using Pymol software. (c) the relative positions of the enzyme active site (highlighted in yellow) and the second receptor binding site (highlighted in blue and red: 366–373, 399–404, 430–433) at the head region of each NA monomer are shown, with the red area (364, 367, 369, 400, 403, 432) denoting the contact site of the second receptor binding site of NA. The location of the D151G mutation is illustrated in green. Each monomer binds to an α-2,3 sialic acid (SA). The NA structure displayed in the figure was obtained from the Protein Data Bank (PDB:4GZW), and the protein model was generated using Pymol software.

Figure 2. The sequence of the three loops (residues 366 to 373), 400 loop (residues 399 to 404), and 430 loop (residues 430 to 433) that form the second receptor binding site of the N1, N2, and N9 in humans and birds. This Seqlogo was generated by the WebLogo program (http://weblogo.berkeley.edu/logo.cgi) using strains retrieved from the GenBank database.

Table 1. Molecular markers associated with receptor-binding properties of NA.

	Mutant	Subtypes	Function	Host	Refs
2SBS	N367S	H2N2/N2	A single reversion to the avian-virus-like sequence (N367S) restores Hemadsorption	Human	[49]
	N400S W403R	H2N2/N2	Affect the hemadsorption activity	Human	[49]
	T401A	H7N9/N9	Substrate binding via this site enhances NA catalytic activity	Human	[46]
	S366N	H1N1/N1	Increase viral NA enzyme activity	Human	[52]
	S366D
	K432E		α-2,6 SA, Enhance NA catalytic activity for a human virus	Human	[27]
	N369H TN368/369DS K432E	H5N1/N1 H1N1/N1	Affect the cleavage of fetuin-linked glycans	Avian Human	[43]
	S372N	H1N1/N1	S372N has the major effect on the 6′SLN-LC-2SBS binding	Human	[40]
	S430G	H5N1/N1	α-2,6 SA, NA S430G mutation plays a role in the affinity to human-type receptors	Human	[68]
NA	D151G	H3N2/N2	α-2,6 SA, Receptor binding properties	MDCK cell passage/ Human	[3,60,61]
	T148I			Human	[5,61]
	E119V			Human	[5]
	H150R	H3N2/N2	α-2,6 SA, NA-mediated agglutination of turkey RBCs	Human	[58,61]
	G147R	H3N2/N2	Receptor binding properties	Avian Human	[50,51]
		H1N1/N1
		H5N1/N1

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Data availability statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.