Objective
Glycosaminoglycans (GAGs) are polysulfated linear polysaccharides with a wide range of biological functions, including a key role in the immune response. Protein-GAG interactions are mostly electrostatic in nature, mediated by contacts between the negative ly charged groups of GAGs and positively charged amino acid side-chains. Consequently, oligosaccharides in protein-GAG complexes do not occupy hydrophobic pockets, but sit on the protein surface with only a few intermolecular contacts, making conformational analysis and binding studies challenging. Despite their biological significance, at present an atomic level of detail for protein-heparin complexes is provided by a limited number of crystal structures and NMR studies (where heparin is used as a model fo r more-heterogeneous GAGs), whilst the experimental conformations of free GAGs in solution have been exclusively obtained by NMR.
These studies suggest that typically 4-6 carbohydrate rings are in close contact with the protein surface and in the majority of cases, helical conformations very close to those found for free heparin in solution are preserved. However, models of GAG-protein complexes are emerging that involve much longer chains and/or their interactions spanning several protein subunits. Two approaches to the selective chemical functionalisation (tagging) of GAGs will be used by the EIF Fellow; using new synthetic methodology recently developed at Edinburgh.
In the first, the dual introduction of fluorescent labels will allow conformational studies of GAGs in solution, and bound to proteins, by time-resolved fluorescence resonance energy transfer (TR-FRET). In the second, the attachment of paramagnetic moieties to either the reducing, or non-reducing, end of GAGs, and observation of the effect of this on protein atoms by NMR, will allow distances between the two molecules to be inferred and the binding position of the GAG oligosaccharide on a protein surface to be determined.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology materials engineering crystals
- medical and health sciences clinical medicine ophthalmology
- natural sciences biological sciences biochemistry biomolecules carbohydrates
- natural sciences chemical sciences organic chemistry amines
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2005-MOBILITY-5
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
EDINBURGH
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.