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Two glycosylation sites in H5N1 influenza virus hemagglutinin that affect binding preference by computer-based analysis.

Chen W, Sun S, Li Z - PLoS ONE (2012)

Bottom Line: Two glycosylation sites, 158N and 169N, also participate in receptor recognition.As the SA-α-2,3-Gal and SA-α-2,6-Gal receptor adopted two distinctive topologies, straight and fishhook-like, respectively, the presence of N-glycans at 158N would decrease the affinity of HA for all of the receptors, particularly SA-α-2,6-Gal analogs.The steric clashes of the huge glycans shown at another glycosylation site, 169N, located on an adjacent HA monomer, would be more effective in preventing the binding of SA-α-2,3-Gal analogs.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Xi'an, People's Republic of China.

ABSTRACT
Increasing numbers of H5N1 influenza viruses (IVs) are responsible for human deaths, especially in North Africa and Southeast Asian. The binding of hemagglutinin (HA) on the viral surface to host sialic acid (SA) receptors is a requisite step in the infection process. Phylogenetic analysis reveals that H5N1 viruses can be divided into 10 clades based on their HA sequences, with most human IVs centered from clade 1 and clade 2.1 to clade 2.3. Protein sequence alignment in various clades indicates the high conservation in the receptor-binding domains (RBDs) is essential for binding with the SA receptor. Two glycosylation sites, 158N and 169N, also participate in receptor recognition. In the present work, we attempted to construct a serial H5N1 HA models including diverse glycosylated HAs to simulate the binding process with various SA receptors in silico. As the SA-α-2,3-Gal and SA-α-2,6-Gal receptor adopted two distinctive topologies, straight and fishhook-like, respectively, the presence of N-glycans at 158N would decrease the affinity of HA for all of the receptors, particularly SA-α-2,6-Gal analogs. The steric clashes of the huge glycans shown at another glycosylation site, 169N, located on an adjacent HA monomer, would be more effective in preventing the binding of SA-α-2,3-Gal analogs.

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Related in: MedlinePlus

The docking complexes between six HAs and eight sialoglycans.SA-α-2,3-Gal receptors are superimposed with distal SA residues at left, whereas the SA-α-2,6-Gal receptors are superimposed with distal SA residues at right. LSTa/LSTc are shown in blue, 3DSLNT/6DSLNT are shown in green, BM3/BM6 are shown in red and BG3/BG6 are shown in yellow. The types of receptors deploy distinctive topologies: most SA-α-2,3-Gal receptors are straight and extrorse, whereas the SA-α-2,6-Gal receptors are fishhook-like and ental. (A) 03HK-sialoglycan docking complexes, (B) 04VN-sialoglycan docking complexes, (C) MG-sialoglycan docking complexes, (D) HM-sialoglycan docking complexes, (E) DS-sialoglycan docking complexes, (F) FG-sialoglycan docking complexes.
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pone-0038794-g007: The docking complexes between six HAs and eight sialoglycans.SA-α-2,3-Gal receptors are superimposed with distal SA residues at left, whereas the SA-α-2,6-Gal receptors are superimposed with distal SA residues at right. LSTa/LSTc are shown in blue, 3DSLNT/6DSLNT are shown in green, BM3/BM6 are shown in red and BG3/BG6 are shown in yellow. The types of receptors deploy distinctive topologies: most SA-α-2,3-Gal receptors are straight and extrorse, whereas the SA-α-2,6-Gal receptors are fishhook-like and ental. (A) 03HK-sialoglycan docking complexes, (B) 04VN-sialoglycan docking complexes, (C) MG-sialoglycan docking complexes, (D) HM-sialoglycan docking complexes, (E) DS-sialoglycan docking complexes, (F) FG-sialoglycan docking complexes.

Mentions: Commonly, the SA in α-2,3-sialoglycans and α-2,6-sialoglycans adopt the trans or cis conformation, respectively, which is oriented to the 158N glycosylation site [12], [27]. In all of the docking complexes, the carboxylate, hydroxyl, N-acetyl and glycerol groups in SA buried inside the shallow pocket (Figure 7). This reflected that HA, as a kind of glycan-binding protein (GBP), had a natural tendency to bind SA. The penultimate Gal were distinctive based on the preference of HA, as not all of the Gals would fit into the RBD due to the steric clashes of amino-acid residues or N-glycan, much less the antepenultimate GlcNAc/Man in receptors. Most antepenultimate residues would form a β1-3 or β1-4 glycosidic linkage with the penultimate β-D-Gal. As a result, the α-2,3-sialoglycan and α-2,6-sialoglycan conformations were predominantly straight and fishhook-like, respectively (Figure S1, S2). The topologies of the α-2,3-sialoglycans was extrorse, whereas the α-2,6-sialoglycans, which lean toward Helix190, were ental.


Two glycosylation sites in H5N1 influenza virus hemagglutinin that affect binding preference by computer-based analysis.

Chen W, Sun S, Li Z - PLoS ONE (2012)

The docking complexes between six HAs and eight sialoglycans.SA-α-2,3-Gal receptors are superimposed with distal SA residues at left, whereas the SA-α-2,6-Gal receptors are superimposed with distal SA residues at right. LSTa/LSTc are shown in blue, 3DSLNT/6DSLNT are shown in green, BM3/BM6 are shown in red and BG3/BG6 are shown in yellow. The types of receptors deploy distinctive topologies: most SA-α-2,3-Gal receptors are straight and extrorse, whereas the SA-α-2,6-Gal receptors are fishhook-like and ental. (A) 03HK-sialoglycan docking complexes, (B) 04VN-sialoglycan docking complexes, (C) MG-sialoglycan docking complexes, (D) HM-sialoglycan docking complexes, (E) DS-sialoglycan docking complexes, (F) FG-sialoglycan docking complexes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375263&req=5

pone-0038794-g007: The docking complexes between six HAs and eight sialoglycans.SA-α-2,3-Gal receptors are superimposed with distal SA residues at left, whereas the SA-α-2,6-Gal receptors are superimposed with distal SA residues at right. LSTa/LSTc are shown in blue, 3DSLNT/6DSLNT are shown in green, BM3/BM6 are shown in red and BG3/BG6 are shown in yellow. The types of receptors deploy distinctive topologies: most SA-α-2,3-Gal receptors are straight and extrorse, whereas the SA-α-2,6-Gal receptors are fishhook-like and ental. (A) 03HK-sialoglycan docking complexes, (B) 04VN-sialoglycan docking complexes, (C) MG-sialoglycan docking complexes, (D) HM-sialoglycan docking complexes, (E) DS-sialoglycan docking complexes, (F) FG-sialoglycan docking complexes.
Mentions: Commonly, the SA in α-2,3-sialoglycans and α-2,6-sialoglycans adopt the trans or cis conformation, respectively, which is oriented to the 158N glycosylation site [12], [27]. In all of the docking complexes, the carboxylate, hydroxyl, N-acetyl and glycerol groups in SA buried inside the shallow pocket (Figure 7). This reflected that HA, as a kind of glycan-binding protein (GBP), had a natural tendency to bind SA. The penultimate Gal were distinctive based on the preference of HA, as not all of the Gals would fit into the RBD due to the steric clashes of amino-acid residues or N-glycan, much less the antepenultimate GlcNAc/Man in receptors. Most antepenultimate residues would form a β1-3 or β1-4 glycosidic linkage with the penultimate β-D-Gal. As a result, the α-2,3-sialoglycan and α-2,6-sialoglycan conformations were predominantly straight and fishhook-like, respectively (Figure S1, S2). The topologies of the α-2,3-sialoglycans was extrorse, whereas the α-2,6-sialoglycans, which lean toward Helix190, were ental.

Bottom Line: Two glycosylation sites, 158N and 169N, also participate in receptor recognition.As the SA-α-2,3-Gal and SA-α-2,6-Gal receptor adopted two distinctive topologies, straight and fishhook-like, respectively, the presence of N-glycans at 158N would decrease the affinity of HA for all of the receptors, particularly SA-α-2,6-Gal analogs.The steric clashes of the huge glycans shown at another glycosylation site, 169N, located on an adjacent HA monomer, would be more effective in preventing the binding of SA-α-2,3-Gal analogs.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Xi'an, People's Republic of China.

ABSTRACT
Increasing numbers of H5N1 influenza viruses (IVs) are responsible for human deaths, especially in North Africa and Southeast Asian. The binding of hemagglutinin (HA) on the viral surface to host sialic acid (SA) receptors is a requisite step in the infection process. Phylogenetic analysis reveals that H5N1 viruses can be divided into 10 clades based on their HA sequences, with most human IVs centered from clade 1 and clade 2.1 to clade 2.3. Protein sequence alignment in various clades indicates the high conservation in the receptor-binding domains (RBDs) is essential for binding with the SA receptor. Two glycosylation sites, 158N and 169N, also participate in receptor recognition. In the present work, we attempted to construct a serial H5N1 HA models including diverse glycosylated HAs to simulate the binding process with various SA receptors in silico. As the SA-α-2,3-Gal and SA-α-2,6-Gal receptor adopted two distinctive topologies, straight and fishhook-like, respectively, the presence of N-glycans at 158N would decrease the affinity of HA for all of the receptors, particularly SA-α-2,6-Gal analogs. The steric clashes of the huge glycans shown at another glycosylation site, 169N, located on an adjacent HA monomer, would be more effective in preventing the binding of SA-α-2,3-Gal analogs.

Show MeSH
Related in: MedlinePlus