Membrane protein structural biology in the era of single particle cryo-EM

In the past few years, significant technological breakthroughs in single particle cryo-electron microscopy enabled a 'resolution revolution' of this technique. It also changed structural biology in an unprecedented way. For many biological macromolecules, obtaining well-ordered crystals of suitable size is no longer a prerequisite for determining their atomic structures. One of the most impacted areas is the structural biology of integral membrane proteins. New structures are now determined at a rapid pace. Despite these advances, further technological developments are still required to overcome new technical challenges that face membrane protein structural biology. In this review, I attempt to discuss some of these challenges.