tetano
Editor, Senior Moderator
OMICS. 2013 Jun;17(6):297-301. doi: 10.1089/omi.2012.0107.
Structural Insights on the Potential Significance of the Twin Asn-Residue Found at the Base of the Hemagglutinin 2 Stalk in All Influenza A H1N1 Strains: A Computational Study with Clinical Implications.
Cueno ME, Imai K, Ochiai K.
Source
Department of Microbiology, Division of Immunology and Pathobiology, Dental Research Center, Nihon University School of Dentistry , Tokyo, Japan .
Abstract
Abstract Influenza hemagglutinin (HA) is a homotrimeric glycoprotein responsible for binding to sialic acids found in the host cell surface. HA has a prominent 75 ?-long α-helix (HA2 stalk) that contributes to overall HA structural stability. Among the H1N1 strains, a high level of predicted disorder is found at the base of the HA2 stalk, predominantly containing Asn residues. Surprisingly, the significance of Asn residues at the base of the HA2 stalk has not been elucidated. In this study, we analyzed the HA2 stalk base of 2830 amino acid sequences of the influenza H1N1 subtype obtained from human, swine, and avian strains throughout 1918-2012. We detected a structurally conserved twin Asn-residue (N1452-N1462) present at the HA2 stalk base in all H1N1 strains. In addition, we found that the twin Asn-residue maintains both a 2.13 ? salt bridge and 11.74 ? 110-helix:B-loop distance measurement in all H1N1 strains studied. Both observations were consistent with known HA crystal structures. Interestingly, amino acid substitutions in either or both residues 1452 and 1462 were found to alter these measurements and, likewise, shift the empirical distribution of HA amino acid residues. Thus, we hypothesize that both the N1452 and N1462 residues found at the HA2 stalk base in all H1N1 strains provide the necessary structural requirements to stabilize the HA protein. More importantly, this would imply that the twin-Asn-residue is an ideal target for anti-influenza therapies.
PMID:
23692362
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/23692362
Structural Insights on the Potential Significance of the Twin Asn-Residue Found at the Base of the Hemagglutinin 2 Stalk in All Influenza A H1N1 Strains: A Computational Study with Clinical Implications.
Cueno ME, Imai K, Ochiai K.
Source
Department of Microbiology, Division of Immunology and Pathobiology, Dental Research Center, Nihon University School of Dentistry , Tokyo, Japan .
Abstract
Abstract Influenza hemagglutinin (HA) is a homotrimeric glycoprotein responsible for binding to sialic acids found in the host cell surface. HA has a prominent 75 ?-long α-helix (HA2 stalk) that contributes to overall HA structural stability. Among the H1N1 strains, a high level of predicted disorder is found at the base of the HA2 stalk, predominantly containing Asn residues. Surprisingly, the significance of Asn residues at the base of the HA2 stalk has not been elucidated. In this study, we analyzed the HA2 stalk base of 2830 amino acid sequences of the influenza H1N1 subtype obtained from human, swine, and avian strains throughout 1918-2012. We detected a structurally conserved twin Asn-residue (N1452-N1462) present at the HA2 stalk base in all H1N1 strains. In addition, we found that the twin Asn-residue maintains both a 2.13 ? salt bridge and 11.74 ? 110-helix:B-loop distance measurement in all H1N1 strains studied. Both observations were consistent with known HA crystal structures. Interestingly, amino acid substitutions in either or both residues 1452 and 1462 were found to alter these measurements and, likewise, shift the empirical distribution of HA amino acid residues. Thus, we hypothesize that both the N1452 and N1462 residues found at the HA2 stalk base in all H1N1 strains provide the necessary structural requirements to stabilize the HA protein. More importantly, this would imply that the twin-Asn-residue is an ideal target for anti-influenza therapies.
PMID:
23692362
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/23692362