Changes in Membrane Protein Structural Biology

SIMPLE SUMMARY: Membrane proteins are essential to all forms of life. Millions of membrane proteins are found in the lipid membrane layer that surrounds cells, and in the lipid membrane layers that surround smaller cellular compartments. Many medicines interact with membrane proteins; these include drugs that treat cancer, heart disease and pain. Research into membrane proteins is therefore important to the design and development of new medicines. Membrane proteins are difficult to work with, partly because they are so small. However, using techniques such as X-ray crystallography and electron microscopy, structural biologists, including those at the Membrane Protein Laboratory, are able to see the atomic detail of membrane proteins. There has been great progress in the field of membrane protein structural biology over the past fifteen years. Here, we review the recent advances in membrane protein structural biology, highlight key methods and give an overview of techniques. We also discuss the challenges that remain in this field, and suggest areas for future research. ABSTRACT: Membrane proteins are essential components of many biochemical processes and are important pharmaceutical targets. Membrane protein structural biology provides the molecular rationale for these biochemical process as well as being a highly useful tool for drug discovery. Unfortunately, membrane protein structural biology is a difficult area of study due to low protein yields and high levels of instability especially when membrane proteins are removed from their native environments. Despite this instability, membrane protein structural biology has made great leaps over the last fifteen years. Today, the landscape is almost unrecognisable. The numbers of available atomic resolution structures have increased 10-fold though advances in crystallography and more recently by cryo-electron microscopy. These advances in structural biology were achieved through the efforts of many researchers around the world as well as initiatives such as the Membrane Protein Laboratory (MPL) at Diamond Light Source. The MPL has helped, provided access to and contributed to advances in protein production, sample preparation and data collection. Together, these advances have enabled higher resolution structures, from less material, at a greater rate, from a more diverse range of membrane protein targets. Despite this success, significant challenges remain. Here, we review the progress made and highlight current and future challenges that will be overcome.