Binding of novel peptides to a new cell membrane target on pancreatic beta cells

Important results from the project

The goal was to assess binding of peptides to a specific receptor using X-ray crystallography methods. The receptor and target protein were produced in laboratory scale. The receptor in complex with peptides were purified and subsequently crystallised to produce well-diffracting crystals. The crystal structure of the receptor was determined in complex with a peptide at 1.55 Å in resolution. The binding has been confirmed using traditional laboratory techniques at LUDC using both the purified protein, commercially available small-scale protein lots and binding on human cells.

Expected long term effects

The determination of the crystal structure of peptide/receptor complex at very high resolution, 1.55 Å in resolution, was successfully achieved. The binding has been confirmed using traditional laboratory techniques at LUDC, with focus on cells and ex vivo material involved in inflammation and tissue repair. Future plans are to assess this binding further using different techniques, to understand the ability of Follicum peptides as potential medical use and explore potential indications. In parallel, Follicum peptides action will be compared with known blockers of the receptor.

Approach and implementation

The receptor in complex with different peptides were purified and subsequently set up for crystallization to produce well-diffracting crystals. Thereafter, data were collected on the I04 beamline at Diamond Light Source, UK. Structural data was analyzed by SBX. Published crystal structures of the receptor were utilized to investigate any corresponding or overlapping binding of other molecules to the same part of the target protein. The structural results obtained were translated to biological function and establishment of mode of action using different in vitro models.