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33.16: Cryo-electron Microscopy

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Cell Biology

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Cryo-electron Microscopy

33.16: Cryo-electron Microscopy

Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for which they won the Nobel Prize in Chemistry in 2017.

X-ray diffraction and nuclear magnetic resonance (NMR) techniques are also used for obtaining high-resolution structures of biomolecules or studying their conformational changes. However, to get the X-ray structure, a molecule needs to be crystallized, which may not be possible every time. Even if a molecule is crystallizable, the crystallization process can alter its biomolecular structure, which is no longer representative of the native structure. Cryo-EM does not require a crystallized sample, and also enables visualization of molecular movements or interactions of biomolecules in their native state. Similarly, NMR technique is only limited to relatively small soluble proteins and is not suited for the non-polar proteins embedded in cell membranes. On the other hand, cryo-EM enables the study of larger proteins, membrane-bound receptors, or biomolecular complexes.

Cryo-EM is extensively being used in biochemistry to study the structure, function, and interaction of biomolecules. The infectious agents, such as viruses, can be identified and studied using cryo-EM. For example, during the Zika virus outbreak in Brazil, cryo-EM was utilized to create a 3D image of the virus structure so that the potential anti-viral drug targets could be identified.


Cryo-electron Microscopy Electron Microscopy Cryo-EM Biological Samples Artifacts High-resolution Images Frozen Samples Electron Beam Damage Nobel Prize In Chemistry X-ray Diffraction Nuclear Magnetic Resonance (NMR) Biomolecular Structure Native State Molecular Movements Biomolecular Complexes

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