Influence of the protein sequence and structure on.. (GLYCAN HETEROGENEITY)
Influence of the protein sequence and structure on the glycan micro-heterogeneity
Date du début: 1 mai 2014,
Date de fin: 30 avr. 2016
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
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