Mechanism of Glycan Receptor Recognition and Specificity Switch for Avian, Swine, and Human Adapted Influenza Virus Hemagglutinins: A Molecular Dynamics Perspective.
Hemagglutinins (HA's) from duck, swine, and human influenza viruses have previously been shown to prefer avian and human glycan receptor analogues with distinct topological profiles, pentasaccharides LSTa (α-2,3 linkage) and LSTc (α-2,6 linkage), in comparative molecular dynamics studies. On the bas...
| Publicado en: | Journal of the American Chemical Society Vol. 131; no. 47; pp. 17430 - 17443 |
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| Autores principales: | , , , , , , , , |
| Formato: | Artículo |
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American Chemical Society
12/2/2009
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| Materias: | |
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=46974716&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 46974716 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 12/2/2009 vid: 131 iid: 47 pid: 997 pub: American Chemical Society artinfo: ui: 46974716 10.1021/ja904052q ppf: 17430 ppct: 13 formats: tig: atl: Mechanism of Glycan Receptor Recognition and Specificity Switch for Avian, Swine, and Human Adapted Influenza Virus Hemagglutinins: A Molecular Dynamics Perspective. aug: au: Newhouse, E. Irene Dong Xu Markwick, Phineus R. L. Amaro, Rommie E. Pao, Hsing C. Wu, Kevin J. Alam, Maqsudul McCammon, J. Andrew Li, Wilfred W. affil: Maui High Performance Computing Center, Kihei, Maui, Hawaii 96753 National Biomedical Computation Resource, University of California--San Diego, La Jolla, California 92093-0505 Howard Hughes Medical Institute, University of California-San Diego, La Jolla, California 92093-0365 Department of Chemistry and Biochemistry and NSF Center for Theoretical Biological Physics (CTBP), University of California-San Diego, La Jolla, California 92093-0365 Department of Microbiology, University of Hawaii at Manoa, 2538 McCarthy Mall, Snyder 111, Honolulu, Hawaii 96822 Department of Pharmacology, University of California-San Diego, La Jolla, California su: Influenza Respiratory infections Hemagglutinin Immunity Blood agglutination Preventive medicine sug: subj: Influenza Respiratory infections Hemagglutinin Immunity Blood agglutination Preventive medicine ab: Hemagglutinins (HA's) from duck, swine, and human influenza viruses have previously been shown to prefer avian and human glycan receptor analogues with distinct topological profiles, pentasaccharides LSTa (α-2,3 linkage) and LSTc (α-2,6 linkage), in comparative molecular dynamics studies. On the basis of detailed analyses of the dynamic motions of the receptor binding domains (RBDs) and interaction energy profiles with individual glycan residues, we have identified ~30 residue positions in the RBD that present distinct profiles with the receptor analogues. Glycan binding constrained the conformational space sampling by the HA. Electrostatic steering appeared to play a key role in glycan binding specificity. The complex dynamic behaviors of the major SSE and trimeric interfaces with or without bound glycans suggested that networks of interactions might account for species specificity in these low affinity and high avidity (multivalent) interactions between different HA and glycans. Contact frequency, energetic decomposition, and H-bond analyses revealed species-specific differences in HA--glycan interaction profiles, not readily discernible from crystal structures alone. Interaction energy profiles indicated that mutation events at the set of residues such as 145, 156, 158, and 222 would favor human or avian receptor analogues, often through interactions with distal asialo-residues. These results correlate well with existing experimental evidence, and suggest new opportunities for simulation-based vaccine and drug development. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2009 holdings: @attributes: islocal: N |
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