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Antigen-Antibody docking reveals the molecular basis for cross-reactivity of the 1918 and 2009 Influenza A/H1N1 pandemic viruses.

Cherian S, Shil P, Mishra AC - Bioinformation (2011)

Bottom Line: Our studies revealed that 2D1 binds to the 2009 HA at antigenic site 'Sa', with stabilizing contacts, similar to that in an available co-crystal structure of 2D1-1918 HA.However, 2D1 failed to bind to the known antigenic sites in the HAs of seasonal strains.Our study thus reveals the molecular basis for pre-existing immunity in elderly people to the 2009 pandemic virus.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics and Data management Division, National Institute of Virology, 20 A, Dr. Ambedkar Road, Pune - 411001,India.

ABSTRACT
To understand the reported cross-reactivity of the 2009 H1N1 and the 1918 H1N1 pandemic viruses we docked the crystal structure of 2D1, an antibody derived from a survivor of the 1918 pandemic, to the structures of hemaglutinin (HA) of the 2009 strain and seasonal H1 vaccine strains. Our studies revealed that 2D1 binds to the 2009 HA at antigenic site 'Sa', with stabilizing contacts, similar to that in an available co-crystal structure of 2D1-1918 HA. However, 2D1 failed to bind to the known antigenic sites in the HAs of seasonal strains. Our study thus reveals the molecular basis for pre-existing immunity in elderly people to the 2009 pandemic virus.

No MeSH data available.


Related in: MedlinePlus

Docking positions of 2D1 antibody with HA protein monomers fromPR1934 and BR2007 obtained using the ZDOCK program. These positions arephysically unrealistic orientations because under normal physiologicalconditions the interfacing residues on the antigen are embedded in the core ofHA trimer. The HA proteins are shown in Orange color, Heavy and light chainsare colored in Blue and Cyan respectively.
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Figure 2: Docking positions of 2D1 antibody with HA protein monomers fromPR1934 and BR2007 obtained using the ZDOCK program. These positions arephysically unrealistic orientations because under normal physiologicalconditions the interfacing residues on the antigen are embedded in the core ofHA trimer. The HA proteins are shown in Orange color, Heavy and light chainsare colored in Blue and Cyan respectively.

Mentions: Docking of 2D1 onto the crystal structure of CA2009 HA was carried out todetermine the binding site and the residues interacting within the antigenantibodycomplex through hydrogen bonds (H-bonds) and salt bridges. The2D1 antibody docked into the Sa antigenic site of CA2009 HA. However, incomparison with SC1918 HA-2D1 co-crystal, some changes were observed inthe orientation of the antibody (Figure 1A). The antibody formed three Hbondsand one salt bridge with the HA residues within the Sa site, and fivehydrogen bonds and one salt bridge outside the Sa site in the 2D1-CA2009 HAcomplex (see Table 1). When compared with theSC1918 HA-2D1 co-crystal, within the Sa site, the H-bonds formed by 166Kand 167S with the 2D1 light chain and the salt bridge between 166K and 93Din the 2D1 light chain were retained in the CA2009 HA-2D1 complex (Figure 1B, see Table 1). Outside the Sa site, the H-bondbetween 126S and 93D was retained. The changed orientation in CA2009 HA-2D1 complex enabled formation of new H-bonds between 119E and 58Y in theheavy chain complementarity determining region 2 (HCDR2) and 95D in thelight chain CDR3 (LCDR3) and 171D with 94S in LCDR3. Salt bridges wereformed by 123K and 54D in HCDR2; 166K and 93D in LCDR3. The mutationN171D in CA2009 facilitated the new H-bond formed by 171D. On the otherhand, when the docking of 2D1 on to the HA of BR2007 and PR1934 wascarried out, the antibody could not recognize antigenic site Sa or other knownantigenic sites (Figure 2). In case of BR2007 the docking program returned acomplex wherein the antibody formed three H-bonds between 246E and 57Y ofthe 2D1 heavy chain, 170N and 32T (in 2D1 light chain) and 125S and 94S (in2D1 light chain). In case of PR1934, the antibody formed three H-bondsbetween 215P and G100, 212R and 54D and 201Y and 54D all in the 2D1heavy chain.


Antigen-Antibody docking reveals the molecular basis for cross-reactivity of the 1918 and 2009 Influenza A/H1N1 pandemic viruses.

Cherian S, Shil P, Mishra AC - Bioinformation (2011)

Docking positions of 2D1 antibody with HA protein monomers fromPR1934 and BR2007 obtained using the ZDOCK program. These positions arephysically unrealistic orientations because under normal physiologicalconditions the interfacing residues on the antigen are embedded in the core ofHA trimer. The HA proteins are shown in Orange color, Heavy and light chainsare colored in Blue and Cyan respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3064850&req=5

Figure 2: Docking positions of 2D1 antibody with HA protein monomers fromPR1934 and BR2007 obtained using the ZDOCK program. These positions arephysically unrealistic orientations because under normal physiologicalconditions the interfacing residues on the antigen are embedded in the core ofHA trimer. The HA proteins are shown in Orange color, Heavy and light chainsare colored in Blue and Cyan respectively.
Mentions: Docking of 2D1 onto the crystal structure of CA2009 HA was carried out todetermine the binding site and the residues interacting within the antigenantibodycomplex through hydrogen bonds (H-bonds) and salt bridges. The2D1 antibody docked into the Sa antigenic site of CA2009 HA. However, incomparison with SC1918 HA-2D1 co-crystal, some changes were observed inthe orientation of the antibody (Figure 1A). The antibody formed three Hbondsand one salt bridge with the HA residues within the Sa site, and fivehydrogen bonds and one salt bridge outside the Sa site in the 2D1-CA2009 HAcomplex (see Table 1). When compared with theSC1918 HA-2D1 co-crystal, within the Sa site, the H-bonds formed by 166Kand 167S with the 2D1 light chain and the salt bridge between 166K and 93Din the 2D1 light chain were retained in the CA2009 HA-2D1 complex (Figure 1B, see Table 1). Outside the Sa site, the H-bondbetween 126S and 93D was retained. The changed orientation in CA2009 HA-2D1 complex enabled formation of new H-bonds between 119E and 58Y in theheavy chain complementarity determining region 2 (HCDR2) and 95D in thelight chain CDR3 (LCDR3) and 171D with 94S in LCDR3. Salt bridges wereformed by 123K and 54D in HCDR2; 166K and 93D in LCDR3. The mutationN171D in CA2009 facilitated the new H-bond formed by 171D. On the otherhand, when the docking of 2D1 on to the HA of BR2007 and PR1934 wascarried out, the antibody could not recognize antigenic site Sa or other knownantigenic sites (Figure 2). In case of BR2007 the docking program returned acomplex wherein the antibody formed three H-bonds between 246E and 57Y ofthe 2D1 heavy chain, 170N and 32T (in 2D1 light chain) and 125S and 94S (in2D1 light chain). In case of PR1934, the antibody formed three H-bondsbetween 215P and G100, 212R and 54D and 201Y and 54D all in the 2D1heavy chain.

Bottom Line: Our studies revealed that 2D1 binds to the 2009 HA at antigenic site 'Sa', with stabilizing contacts, similar to that in an available co-crystal structure of 2D1-1918 HA.However, 2D1 failed to bind to the known antigenic sites in the HAs of seasonal strains.Our study thus reveals the molecular basis for pre-existing immunity in elderly people to the 2009 pandemic virus.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics and Data management Division, National Institute of Virology, 20 A, Dr. Ambedkar Road, Pune - 411001,India.

ABSTRACT
To understand the reported cross-reactivity of the 2009 H1N1 and the 1918 H1N1 pandemic viruses we docked the crystal structure of 2D1, an antibody derived from a survivor of the 1918 pandemic, to the structures of hemaglutinin (HA) of the 2009 strain and seasonal H1 vaccine strains. Our studies revealed that 2D1 binds to the 2009 HA at antigenic site 'Sa', with stabilizing contacts, similar to that in an available co-crystal structure of 2D1-1918 HA. However, 2D1 failed to bind to the known antigenic sites in the HAs of seasonal strains. Our study thus reveals the molecular basis for pre-existing immunity in elderly people to the 2009 pandemic virus.

No MeSH data available.


Related in: MedlinePlus