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A role for underlying glycan structure in influenza binding: extending the species specificity paradigm
Author(s) -
Woods Robert J,
Grant Oliver C,
Hadden Jodi A,
Smith Hannah M.K.,
Peng Wenjie,
De Vries Robert,
McBride Ryan,
Paulson James C.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1103.6
Subject(s) - glycan , computational biology , glycomics , biology , chemistry , biochemistry , glycoprotein
Recently, a new source for carbohydrate specificity data has emerged through the extensive development of glycan microarrays. Glycan array screening provides rapid insight into binding specificities, limited only by the number of elements in the array, the largest of which currently contain on the order of 600 members. Although rich in information, array data do not provide direct insight into the 3D structural properties of the glycan‐protein complexes responsible for the observed specificities. Here we employ a new technology [1,2], Computational Carbohydrate Grafting (CCG), to generate 3D models of glycan‐hemagglutinin complexes that provide a structural rationalization for the sometimes perplexing data from glycan array screening. Given a structure for the protein in complex with a minimal binding determinant, CCG can be employed to generate a 3D model of any related glycan bound to the complex, by splicing the additional branches of the glycan into the bound fragment. This virtual approach overcomes many of the experimental challenges associated with generating structures for these complexes. CCG is a high‐throughput screening method that can be readily validated by comparison with specificity data from glycan array screening. We show that CCG predictions explain differences in specificity for a range of sialylated N ‐linked glycans interacting with human and avian influenza hemagglutinins. The analysis suggests that glycans with poly‐LacNAc extensions can bind in a bidentate fashion to the trimeric HA, consistent with affinity enhancements seen for some hemagglutinins in glycan array data. CGG analysis may prove valuable in elucidating the preferred receptors for influenza adhesion. Support or Funding Information Supported by the National Institutes of Health GM094919 (RJW), and AI050143 & AI099141 (JCP), and the Science Foundation of Ireland 08/IN.1/B2070 (RJW).