{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"Glycan Type Specificity in N-linked Glycosylation: Implications for Highly Glycosylated Viral Surface Proteins","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/11401/78273"},{"label":"dc.language.iso","value":"en_US"},{"label":"dcterms.abstract","value":"Virtually every living cell is covered with glycoproteins. Most mammalian glycoproteins primarily bear N-linked glycans of complex type, having only a small fraction of hybrid glycans and barely any high-mannose glycans. However, some highly glycosylated proteins translated in mammalian cells have an unusually high fraction of high-mannose glycans. The goal of this thesis is to investigate the nature of the mechanisms behind this unusual distribution of glycan types and glycan type specificity for glycosylation sites.  A well-studied example of the abnormally glycosylated protein is HIV envelope glycoprotein gp120, which usually has about 24 glycans, approximately half of them being of high-mannose or hybrid type. We began this project with a statistical analysis of the distribution of gp120 glycan types, which led to finding certain patterns with respect to primary, secondary and tertiary structure of the protein.  Further, in order to develop a mechanistic understanding of the origin of these differences, we developed a stochastic chemical-kinetic model of the N-linked glycosylation pathway in the Golgi Apparatus. This model provides an understanding of how the distribution of glycan types is influenced by three different factors: 1) concentration of glycans in the Golgi Apparatus; 2) input to the Golgi Apparatus; and 3) chemical-kinetic parameters of the system.  Additionally, we have performed a logical analysis of glycan processing in the Endoplasmic Reticulum. This analysis has shown a very limited potential influence of the ER on the final glycan structure, though we did find some parameters of the system that might lead to different output from the ER and therefore different input to the Golgi.  As the main result of this research, we conclude that the most likely reason for the unusually high fraction of high-mannose glycans on certain glycoproteins is indeed the increased overall concentration of glycans. Furthermore, the most likely factor influencing glycan type specificity for certain glycosylation sites is differences in binding affinity of glycans with the ManI enzyme (and perhaps several other enzymes) caused by the secondary and tertiary structure of the protein. We suggest structural research be performed in order to further investigate our conclusions."},{"label":"dcterms.available","value":"2018-06-21T13:38:49Z"},{"label":"dcterms.contributor","value":"Green, David F"},{"label":"dcterms.creator","value":"Krantesvich, Artem"},{"label":"dcterms.dateAccepted","value":"2018-06-21T13:38:49Z"},{"label":"dcterms.dateSubmitted","value":"2018-06-21T13:38:49Z"},{"label":"dcterms.description","value":"Department of Applied Mathematics and Statistics"},{"label":"dcterms.extent","value":"95 pg."},{"label":"dcterms.format","value":"Monograph"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/11401/78273"},{"label":"dcterms.issued","value":"2017-12-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2018-06-21T13:38:49Z (GMT). No. of bitstreams: 1\nKrantesvich_grad.sunysb_0771E_13611.pdf: 3139321 bytes, checksum: 063920668ecf69ad234cc03d8a8a0a95 (MD5)\n  Previous issue date:   12"},{"label":"dcterms.subject","value":"Cytology"},{"label":"dcterms.title","value":"Glycan Type Specificity in N-linked Glycosylation: Implications for Highly Glycosylated Viral Surface Proteins"},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/16%2F36%2F54%2F163654317586271248731432276120421778570/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/16%2F36%2F54%2F163654317586271248731432276120421778570","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}