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In Meso Crystallogenesis of GPCR-protein ligand complexes

Project information

Grant agreement ID: 254103

Status

Closed project

  • Start date

    1 August 2010

  • End date

    31 July 2012

Funded under:

FP7-PEOPLE

  • Overall budget:

    € 238 782,80

  • EU contribution

    € 238 782,80

Coordinated by:

THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

Ireland

Objective

G protein-coupled receptor (GPCR) proteins are the single largest drug target, representing 30% of all marketed drugs. All GPCRs share a basic structural core of seven transmembrane alpha-helical domains. In spite of this similarity, GPCRs have evolved to be extremely versatile receptors for extracellular messengers as diverse as biogenic amines, purines and nucleic acid derivatives, lipids, peptides and proteins, odorants, pheromones, tastants, ions like calcium and protons, and even photons. Due to their significant effect on human physiology and disease, it is crucial to understand from a structural biology perspective, the molecular basis for the interaction between a GPCR and its ligand. The recent success in the structure determination of the Beta2-adrenergic GPCR and the adenosine A2a GPCR using the in meso crystallization methodolgy paves the way for further advances in structure determination of GPCR structures. As of today, there is no structural information available that helps us in understanding the molecular basis of interaction between a GPCR and its protein ligand. In this application, we propose to perform structure-function studies on two GPCRs, CXCR4 and Formyl Peptide Receptor, that are activated by the polypeptides SDF1 and f-MLF respectively. We propose to use in a synergistic fashion two novel methodologies, the BACMAM system and in meso crystallography, to express, purify and crystallize complexes between CXCR4-SDF1 and FPR-fMLF. Information obtained from the structure determination of these complexes would go a long way in helping us understand the molecular mechanisms responsible for the signal transduction properties of GPCRs that are activated by protein ligands. In addition, this information would also help us in designing and developing better drugs aimed at treating cancer metastases, AIDS and Parkinsons disease.

Coordinator

THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

Address

College Green
2 Dublin

Ireland

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 238 782,80

Administrative Contact

Deirdre Savage (Ms.)

Project information

Grant agreement ID: 254103

Status

Closed project

  • Start date

    1 August 2010

  • End date

    31 July 2012

Funded under:

FP7-PEOPLE

  • Overall budget:

    € 238 782,80

  • EU contribution

    € 238 782,80

Coordinated by:

THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

Ireland