Cryo-EM is a powerful tool, but helical applications can have pitfalls
Edward H Egelman1, Fengbin Wang
1Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22903, USA. egelman@virginia.edu.
Soft Matter
|March 17, 2021
Summary
Cryo-electron microscopy (cryo-EM) shows potential in chemistry but pitfalls exist for helical assemblies. Low-resolution cryo-EM models for protein tubes may be incorrect due to symmetry ambiguities.
Area of Science:
- Structural biology
- Chemistry
- Materials science
Background:
- Cryo-electron microscopy (cryo-EM) is a key technique for determining macromolecular structures.
- Direct electron detectors enable near-atomic resolution imaging of complexes.
- Cryo-EM applications in chemistry and materials science are less established.
Purpose of the Study:
- To analyze polymorphic helical protein tubes using low-resolution cryo-EM.
- To evaluate the accuracy of detailed models for protein-protein interfaces in helical assemblies.
- To highlight potential pitfalls in cryo-EM analysis of helical structures.
Main Methods:
- Low-resolution cryo-electron microscopy (cryo-EM) was used to study helical protein tubes.
- Analysis focused on polymorphic forms and interfaces between protein tetramers.
- Models of helical symmetry were critically assessed for accuracy.
Main Results:
- Detailed models were proposed for interfaces in helical protein tubes.
- Intrinsic ambiguities in helical symmetry determination were identified.
- Many proposed models for helical assemblies were found to be potentially incorrect.
Conclusions:
- Cryo-EM has significant potential in chemistry and materials science.
- Low resolution cryo-EM analysis of helical assemblies carries risks of incorrect modeling.
- Achieving near-atomic resolution is crucial for reliable structural determination of helical assemblies.
