GLYCAN HETEROGENEITY

Influence of the protein sequence and structure on the glycan micro-heterogeneity

Coordinatore	EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZURICH    more  Organization address address: Raemistrasse 101 city: ZUERICH postcode: 8092 contact info Titolo: Prof. Nome: Markus Cognome: Aebi Email: send email Telefono: +41 44 6326413
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

#	participant	country	role	EC contrib. [€]
1	EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZURICH  Organization address address: Raemistrasse 101 city: ZUERICH postcode: 8092 contact info Titolo: Prof. Nome: Markus Cognome: Aebi Email: send email Telefono: +41 44 6326413	CH (ZUERICH)	coordinator	199˙317.60

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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'