Context-Specific Target Definition in Influenza A Virus Hemagglutinin-Glycan Receptor Interactions
Protein-glycan interactions are important regulators of a variety of biological processes, ranging from immune recognition to anticoagulation. An important area of active research is directed toward understanding the role of host cell surface glycans as recognition sites for pathogen protein recepto...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2015
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| Online Access: | http://hdl.handle.net/1721.1/96174 https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0001-9344-0205 https://orcid.org/0000-0002-2085-7840 |
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| author | Raman, Rahul Viswanathan, Karthik Sasisekharan, Ram Shriver, Zachary H. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Raman, Rahul Viswanathan, Karthik Sasisekharan, Ram Shriver, Zachary H. |
| author_sort | Raman, Rahul |
| collection | MIT |
| description | Protein-glycan interactions are important regulators of a variety of biological processes, ranging from immune recognition to anticoagulation. An important area of active research is directed toward understanding the role of host cell surface glycans as recognition sites for pathogen protein receptors. Recognition of cell surface glycans is a widely employed strategy for a variety of pathogens, including bacteria, parasites, and viruses. We present here a representative example of such an interaction: the binding of influenza A hemagglutinin (HA) to specific sialylated glycans on the cell surface of human upper airway epithelial cells, which initiates the infection cycle. We detail a generalizable strategy to understand the nature of protein-glycan interactions both structurally and biochemically, using HA as a model system. This strategy combines a top-down approach using available structural information to define important contacts between glycans and HA, with a bottom-up approach using data-mining and informatics approaches to identify the common motifs that distinguish glycan binders from nonbinders. By probing protein-glycan interactions simultaneously through top-down and bottom-up approaches, we can scientifically validate a series of observations. This in turn provides additional confidence and surmounts known challenges in the study of protein-glycan interactions, such as accounting for multivalency, and thus truly defines concepts such as specificity, affinity, and avidity. With the advent of new technologies for glycomics—including glycan arrays, data-mining solutions, and robust algorithms to model protein-glycan interactions—we anticipate that such combination approaches will become tractable for a wide variety of protein-glycan interactions. |
| first_indexed | 2024-09-23T08:47:57Z |
| format | Article |
| id | mit-1721.1/96174 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:47:57Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/961742022-09-23T14:35:55Z Context-Specific Target Definition in Influenza A Virus Hemagglutinin-Glycan Receptor Interactions Raman, Rahul Viswanathan, Karthik Sasisekharan, Ram Shriver, Zachary H. Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. School of Engineering Koch Institute for Integrative Cancer Research at MIT Shriver, Zachary H. Raman, Rahul Viswanathan, Karthik Sasisekharan, Ram Protein-glycan interactions are important regulators of a variety of biological processes, ranging from immune recognition to anticoagulation. An important area of active research is directed toward understanding the role of host cell surface glycans as recognition sites for pathogen protein receptors. Recognition of cell surface glycans is a widely employed strategy for a variety of pathogens, including bacteria, parasites, and viruses. We present here a representative example of such an interaction: the binding of influenza A hemagglutinin (HA) to specific sialylated glycans on the cell surface of human upper airway epithelial cells, which initiates the infection cycle. We detail a generalizable strategy to understand the nature of protein-glycan interactions both structurally and biochemically, using HA as a model system. This strategy combines a top-down approach using available structural information to define important contacts between glycans and HA, with a bottom-up approach using data-mining and informatics approaches to identify the common motifs that distinguish glycan binders from nonbinders. By probing protein-glycan interactions simultaneously through top-down and bottom-up approaches, we can scientifically validate a series of observations. This in turn provides additional confidence and surmounts known challenges in the study of protein-glycan interactions, such as accounting for multivalency, and thus truly defines concepts such as specificity, affinity, and avidity. With the advent of new technologies for glycomics—including glycan arrays, data-mining solutions, and robust algorithms to model protein-glycan interactions—we anticipate that such combination approaches will become tractable for a wide variety of protein-glycan interactions. National Institute of General Medical Sciences (U.S.) (GM 57073) National Institute of General Medical Sciences (U.S.) (U54 GM62116) Singapore-MIT Alliance for Research and Technology 2015-03-25T15:52:36Z 2015-03-25T15:52:36Z 2009-08 Article http://purl.org/eprint/type/JournalArticle 10745521 http://hdl.handle.net/1721.1/96174 Shriver, Zachary, Rahul Raman, Karthik Viswanathan, and Ram Sasisekharan. “Context-Specific Target Definition in Influenza A Virus Hemagglutinin-Glycan Receptor Interactions.” Chemistry & Biology 16, no. 8 (August 28, 2009): 803–814. © 2009 Elsevier Ltd. https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0001-9344-0205 https://orcid.org/0000-0002-2085-7840 en_US http://dx.doi.org/10.1016/j.chembiol.2009.08.002 Chemistry and Biology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Raman, Rahul Viswanathan, Karthik Sasisekharan, Ram Shriver, Zachary H. Context-Specific Target Definition in Influenza A Virus Hemagglutinin-Glycan Receptor Interactions |
| title | Context-Specific Target Definition in Influenza A Virus Hemagglutinin-Glycan Receptor Interactions |
| title_full | Context-Specific Target Definition in Influenza A Virus Hemagglutinin-Glycan Receptor Interactions |
| title_fullStr | Context-Specific Target Definition in Influenza A Virus Hemagglutinin-Glycan Receptor Interactions |
| title_full_unstemmed | Context-Specific Target Definition in Influenza A Virus Hemagglutinin-Glycan Receptor Interactions |
| title_short | Context-Specific Target Definition in Influenza A Virus Hemagglutinin-Glycan Receptor Interactions |
| title_sort | context specific target definition in influenza a virus hemagglutinin glycan receptor interactions |
| url | http://hdl.handle.net/1721.1/96174 https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0001-9344-0205 https://orcid.org/0000-0002-2085-7840 |
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