Cryo-electron microscopy and the amazing race to atomic resolution

Area of Science:

• Structural Biology
• Biophysics
• Microscopy

Background:

• Cryo-electron microscopy (cryo-EM) is a powerful technique for determining 3D structures of biological specimens.
• Historically, cryo-EM excelled with large, symmetrical, or ordered samples, achieving subnanometer resolution.
• High-resolution analysis of smaller, dynamic, or asymmetric molecules remained a significant challenge.

Purpose of the Study:

• To highlight recent technological and computational advancements in cryo-EM.
• To demonstrate the expanded scope of biological macromolecules amenable to cryo-EM analysis.
• To showcase the potential for achieving atomic resolution structures with cryo-EM.

Main Methods:

• Utilizing advanced electron microscopes with automated data collection.
• Employing direct electron detection cameras for enhanced data quality.
• Applying novel image processing algorithms for improved structural analysis.

Main Results:

• Successful determination of <5 Å resolution 3D structures for challenging samples like membrane proteins.
• Expanded capability to study molecules with low or no symmetry.
• Demonstrated progress towards achieving atomic resolution in cryo-EM studies.

Conclusions:

• Recent innovations have significantly broadened the applicability of cryo-EM.
• Cryo-EM is now capable of resolving complex and previously intractable biological structures.
• The technique is rapidly advancing towards routine atomic resolution determination.