tetano
Editor, Senior Moderator
Biochemistry. 2014 May 30. [Epub ahead of print]
Insights into Human Glycan Receptor conformation of 1918 Pandemic Haemagglutinin-Glycan Complexes derived from NMR and MD studies.
Elli S, Macchi E, Rudd TR, Raman R, Sassaki GL, Viswanathan K, Yates EA, Shriver Z, Naggi A, Torri G, Sasisekharan R, Guerrini M.
Abstract
Glycan receptor binding and specificity of Influenza A viral haemagglutinin are critical for virus infection and transmission in humans. However, ambiguities in the interpretation of the receptor-binding specificity of haemagglutinin from human- and avian-adapted viruses has confounded an understanding of its relationship with aerosol transmissibility, an exclusive property of human-adapted viruses. A previous conformational study, which we performed, indicated that human and avian receptors sample distinct conformations in solution. Based on detailed NMR studies provided herein, we offer evidence on the distinct structural constraints imposed by haemagglutinin receptor binding sites on the glycan conformational space upon binding. The haemagglutinin from the SC18 virus, which has efficient aerosol transmissibility in humans (human adapted), imposed the most stringent constraints on the conformational space of the human glycan receptor (LSTc), compared to single (NY18) or double (AV18) amino acid HA mutants, a property correlating to the ligand-HA binding strength. This relationship was also observed for the avian adapted HA, where the high affinity binding partner, AV18, imposed the most stringent conformational constraints on the avian receptor, compared to NY18. In particular, it is interesting to observe how different HAs when binding to human or avian glycosidic receptors impose significantly different conformational states, in terms of the states sampled by the glycosidic backbone and/or the entire molecule shape (linear or bent), when compared to the corresponding unbound glycans. Significantly, we delineate a 'characteristic NMR signature' for the human adapted haemagglutinin (SC18) binding to human glycan receptors. Therefore, the conformational space constraints imposed by the haemagglutinin receptor binding site provide a characteristic signature that could be a useful tool for surveillance of human adaptation of other (such as H7N9 and H5N1) deadly influenza viruses.
PMID:
24878075
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24878075
Insights into Human Glycan Receptor conformation of 1918 Pandemic Haemagglutinin-Glycan Complexes derived from NMR and MD studies.
Elli S, Macchi E, Rudd TR, Raman R, Sassaki GL, Viswanathan K, Yates EA, Shriver Z, Naggi A, Torri G, Sasisekharan R, Guerrini M.
Abstract
Glycan receptor binding and specificity of Influenza A viral haemagglutinin are critical for virus infection and transmission in humans. However, ambiguities in the interpretation of the receptor-binding specificity of haemagglutinin from human- and avian-adapted viruses has confounded an understanding of its relationship with aerosol transmissibility, an exclusive property of human-adapted viruses. A previous conformational study, which we performed, indicated that human and avian receptors sample distinct conformations in solution. Based on detailed NMR studies provided herein, we offer evidence on the distinct structural constraints imposed by haemagglutinin receptor binding sites on the glycan conformational space upon binding. The haemagglutinin from the SC18 virus, which has efficient aerosol transmissibility in humans (human adapted), imposed the most stringent constraints on the conformational space of the human glycan receptor (LSTc), compared to single (NY18) or double (AV18) amino acid HA mutants, a property correlating to the ligand-HA binding strength. This relationship was also observed for the avian adapted HA, where the high affinity binding partner, AV18, imposed the most stringent conformational constraints on the avian receptor, compared to NY18. In particular, it is interesting to observe how different HAs when binding to human or avian glycosidic receptors impose significantly different conformational states, in terms of the states sampled by the glycosidic backbone and/or the entire molecule shape (linear or bent), when compared to the corresponding unbound glycans. Significantly, we delineate a 'characteristic NMR signature' for the human adapted haemagglutinin (SC18) binding to human glycan receptors. Therefore, the conformational space constraints imposed by the haemagglutinin receptor binding site provide a characteristic signature that could be a useful tool for surveillance of human adaptation of other (such as H7N9 and H5N1) deadly influenza viruses.
PMID:
24878075
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24878075