Highest X-ray resolution for a membrane protein

A team of scientists from the Scripps Research Institute in California and the Leiden/Amsterdam Center for Drug Research has recorded the highest resolution structure to date for a membrane protein, using X-ray diffraction. They studied the human A_2A adenosine receptor (A2A), which is one of the the group of proteins known as the G protein-coupled receptors (GPCRs), and reported their findings in Science.

A2A is an oily substance and difficult to crystallise, so the team replaced its third intracellular loop with the protein apocytochrome b₅₆₂RIL to facilitate crystallisation and achieved a resolution of 1.8Å. This allowed them to make out previously unrecognisable features such as the occurrence of 57 ordered water molecules in clusters, one of which contains a sodium ion. Stabilising cholesterol molecules and trapped lipids were also seen.

GPCRs are targets for many types of drugs and the significance of recent research into this group of proteins is discussed in a recent News release from Scripps.