Cryo-electron microscopy of cholinesterases, present and future

Area of Science:

• Biochemistry
• Structural Biology
• Neuroscience

Background:

• Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are crucial enzymes existing in various oligomeric forms.
• While crystal structures of monomeric AChE and BChE are known, the structures of physiologically relevant tetrameric forms were recently determined.

Purpose of the Study:

• To review the contribution of recent cryo-electron microscopy (cryo-EM) structures to understanding cholinesterase (ChE) oligomerization.
• To highlight the utility of cryo-EM for resolving complex protein assemblies, especially those difficult to express recombinantly.
• To propose future directions in ChE structural biology, focusing on native cellular imaging.

Main Methods:

• Cryo-electron microscopy (cryo-EM) single-particle analysis was employed to determine the structure of ChE tetramers.
• Review of existing literature on ChE structures and oligomerization.

Main Results:

• Cryo-EM has enabled the resolution of previously unknown structures of physiologically relevant ChE tetramers.
• This technique overcomes limitations in recombinant expression for studying complex protein assemblies.

Conclusions:

• Recent cryo-EM structures have significantly advanced the understanding of cholinesterase oligomerization.
• The next frontier involves imaging membrane-anchored ChE oligomers in their native cellular context using advanced imaging techniques.