GLYCAN HETEROGENEITY
Influence of the protein sequence and structure on the glycan micro-heterogeneity
| Coordinatore | EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZURICH
Organization address
address: Raemistrasse 101 contact info |
| Nazionalità Coordinatore | Switzerland [CH] |
| Totale costo | 199˙317 € |
| EC contributo | 199˙317 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2013-IEF |
| Funding Scheme | MC-IEF |
| Anno di inizio | 2014 |
| Periodo (anno-mese-giorno) | 2014-05-01 - 2016-04-30 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZURICH
Organization address
address: Raemistrasse 101 contact info |
CH (ZUERICH) | coordinator | 199˙317.60 |
Mappa
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Obiettivo del progetto (Objective)
'N-glycosylation consists in the addition of a glycan precursor onto a nascent protein in the endoplasmic reticulum. This glycan is then trimmed and matured in the Golgi by addition of various sugars motifs, leading to a large heterogeneity of glycans structures, from site to site or on the same glycosylation site. Until now the underlying causes of this micro-heterogeneity have not clearly been identified and the influence of the sugar-nucleotides pool and the glycosyltransferases present in the cell was proposed. By using high-performance technologies such as mass spectrometry (LC-MS-MS), NMR and crystallography, and by using classic biochemical and molecular biology approaches to modify the glycan and/ or the structure of a set of model proteins, we propose here to prove that heterogeneity of glycan structures is also highly influenced by the three-dimensional protein structure and the interaction between the protein and the glycan. Since glycosylation can be involved in protein: folding, maturation, secretion and/or functions, the appreciation of heterogeneity mechanism is crucial to better apprehend the role of the glycans at a cellular level. In addition of paving the way to a better comprehension of the glycan structures role , this challenging project will impact European pharmaceutical company producing recombinant glycoproteins or glycopeptides as drugs, by giving them answers on how to reduce the glycan heterogeneity without multiplying high-cost purification steps.
Keywords: glycosylation; biochemistry; recombinant protein'