title: An airborne transmissible avian influenza H5 hemagglutinin seen at the atomic level.
abstract: Recent studies have identified several mutations in the hemagglutinin (HA) protein that allow the highly pathogenic avian H5N1 influenza A virus to transmit between mammals by airborne route. Here, we determined the complex structures of wild-type and mutant HAs derived from an Indonesia H5N1 virus bound to either avian or human receptor sialic acid analogs. A cis/trans conformational change in the glycosidic linkage of the receptor analog was observed, which explains how the H5N1 virus alters its receptor-binding preference. Furthermore, the mutant HA possessed low affinities for both avian and human receptors. Our findings provide a structural and biophysical basis for the H5N1 adaptation to acquire human, but maintain avian, receptor-binding properties.
authors: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors: Wei
authors: W
authors: Zhang
authors: Yi
authors: Y
authors: Shi
authors: Xishan
authors: X
authors: Lu
authors: Yuelong
authors: Y
authors: Shu
authors: Jianxun
authors: J
authors: Qi
authors: George F
authors: GF
authors: Gao
mesh_terms: D000818:Animals; D001665:Binding Sites; D001717:Birds; D002236:Carbohydrate Conformation; D018360:Crystallography, X-Ray; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D055550:Protein Stability; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D050505:Mutant Proteins; D009844:Oligosaccharides; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D011994:Recombinant Proteins; C109963:hemagglutinin, avian influenza A virus; C092488:sialic acid receptor; C016735:sialooligosaccharides