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

Abstract

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.

Figure 1.. Increase of number of cryo-EM structure of membrane proteins

This graph shows the percentage of cryo-EM membrane protein structures in every year since 2005. The percentage increase to close to 40% in the first three months of 2018. It shows an increasing role of single particle cryo-EM in structural biology of membrane proteins.

Figure 2.. Cryo-EM structures of TRPM

In December 2017, three structures of TRPM4, including human TRPM4 with and without Ca2+ bound [34], mouse TRPM4 with and without ATP bound [69], human TRPM4 with decavanadate bound [70] and one structure of TRPM8 [75] were published in the same week. Another structure of human TRPM4 apo structure was [68] published two months later. Structure information of all these works are complementary with each other, provide substantial amount of structural information of this subfamily of TRP channel.