Proteins for better health

A team of UK scientists has made an important development that will help the design of new drugs for many conditions.

Modern medicine relies on drugs that are often designed to latch onto proteins on the surface of cells. Many of these drugs target recombinant G protein-couple receptors (GPCRs), which detect chemical signals outside a cell and trigger a response.

The team succeeded using a new approach called conformational stabilisation, trapping the receptor in a form bound to a betablocker – drugs that target receptors to slow down heart rates. The researchers were able to stabilise the receptor proteins long enough to obtain crystals.

UK researchers, thanks to an STFC subscription, can use one of the largest synchrotrons in the world, the European Synchrotron Radiation Facility (ESRF) in France. The crystals, under an exceptionally small beam of X-rays, revealed the structure of the adrenalin stress hormone receptor (ß1 adrenergic receptor), which regulates heart rate and blood pressure.

Drugs used in asthma inhalers target a similar adrenergic receptor, ß2, to dilate the bronchial muscles in the lung and airways. But some drugs can affect both receptors. An inhaler which treats an asthma attack, for example, might also raise the heart beat. By comparing the two receptors, scientists could now target drugs to avoid these side effects as well as discover new drugs for other diseases.

• GPCRs allow us to process light, smells and regulate our behaviour, mood and immune response.
  
  
• GPCRs play a crucial role in many diseases.
  
  
• The MRC spin-out company founded in 2007, Heptares Therapeutics Ltd, secured £21 million of equity finance in 2008-2009 to speed up the development of smallmolecule drug candidates for treating diseases.