Molecular characterization of the receptor binding structure-activity relationships of influenza B virus hemagglutinin

Carbone, V., Kim, H., Huang, J. X., Baker, M. A., Ong, C., Cooper, M. A., Li, J., Rockman, S. and Velkov, T. (2013) Molecular characterization of the receptor binding structure-activity relationships of influenza B virus hemagglutinin. Acta Virologica, 57 3: 313-332. doi:10.4149/av_2013_03_313

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Author Carbone, V.
Kim, H.
Huang, J. X.
Baker, M. A.
Ong, C.
Cooper, M. A.
Li, J.
Rockman, S.
Velkov, T.
Title Molecular characterization of the receptor binding structure-activity relationships of influenza B virus hemagglutinin
Journal name Acta Virologica   Check publisher's open access policy
ISSN 0001-723X
1336-2305
Publication date 2013-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.4149/av_2013_03_313
Volume 57
Issue 3
Start page 313
End page 332
Total pages 20
Place of publication Bratislava, Slovakia
Publisher AEPress, s.r.o.
Language eng
Formatted abstract
Selectivity of α2,6-linked human-like receptors by B hemagglutinin (HA) is yet to be fully understood. This study integrates binding data with structure-recognition models to examine the impact of regional-specific sequence variations within the receptor-binding pocket on selectivity and structure activity relationships (SAR). The receptor-binding selectivity of influenza B HAs corresponding to either B/Victoria/2/1987 or the B/Yamagata/16/88 lineages was examined using surface plasmon resonance, solid-phase ELISA and gel-capture assays. Our SAR data showed that the presence of asialyl sugar units is the main determinant of receptor preference of α2,6 versus α2,3 receptor binding. Changes to the type of sialyl-glycan linkage present on receptors exhibit only a minor effect upon binding affinity. Homology-based structural models revealed that structural properties within the HA pocket, such as a glyco-conjugate at Asn194 on the 190-helix, sterically interfere with binding to avian receptor analogs by blocking the exit path of the asialyl sugars. Similarly, naturally occurring substitutions in the C-terminal region of the 190-helix and near the N-terminal end of the 140-loop narrows the horizontal borders of the binding pocket, which restricts access of the avian receptor analog LSTa. This study helps bridge the gap between ligand structure and receptor recognition for influenza B HA; and provides a consensus SAR model for the binding of human and avian receptor analogs to influenza B HA.
Keyword Influenza B
Receptor Binding
Structure activity relationships
Egg Adaptation
Specificity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
 
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