A StaR is a stabilised GPCR containing a small number of point mutations that greatly improve its thermostability without disrupting its pharmacology. StaR technology is transferrable across GPCR families and allows the selection of stable, functionally relevant, purified conformations of target GPCRs that retain their expected drug-binding characteristics.
The StaR technology is based on world-class science from the MRC Laboratory of Molecular Biology (Cambridge, UK), with which Heptares maintains exclusive consultancies and active collaboration.
In addition, Heptares has access to all IP generated from LMB relating to the application of the StaR technology to GPCRs and other transmembrane proteins.
Complex of the human beta 2 adrenergic receptor and an antibody fragment
Acknowledgements:
Rasmussen et al. Nature. 2007 Nov 15;450(7168):383-7
Electron density around the cyanopindolol ligand binding site in the beta 1 adrenergic receptor.
Acknowledgements:
Warne et al, Nature. 2008 Jul 24;454(7203):486-91
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Crystal of a stabilised beta 1 adrenergic receptor
Acknowledgements:
Tony Warne, Maria Serrano Vega, Rouslan Moukhametzianov
Chris Tate and Gebhard F X Schertler Laboratory of Molecular Biology Cambridge
Electron density map of bovine rhodopsin. Krebs, A., Edwards, P.C, Villa, C., Li, J. and Schertler, G.F.X
The three-dimensional structure of bovine rhodopsin determined by electron cryomicroscopy. J. Biol. Chem. 278, 50217-50225 (2003)
Model of the crystal structure of bovine rhodopsin showing site of retinal binding
Acknowledgements:
Li J et al. J Mol Biol. 2004 Nov 5;343(5):1409-38
Structure of the beta1 adrenergic receptor.
Acknowledgements:
Warne et al, Nature. 2008 Jul 24;454(7203):486-91
Crystal packing of the beta 1 adrenergic receptor.
Acknowledgements:
Nature. 2008 Jul 24;454(7203):486-91.
Model of the cyanopindolol binding site in the beta 1 adrenergic receptor showing the interactions of the drug with the side chains of the receptor protein.
Acknowledgements.
Warne et al, Nature. 2008 Jul 24;454(7203):486-91
The StaR™ creation process involves multiple iterations of mutagenesis of the receptor until the thermostability of the protein reaches a level that allows it to be easily manipulated. At this point the StaR can be produced in larger quantities and purified for protein-ligand crystallography and screening applications.
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