Cryo TEM | Krios Cryo TEM Applications | Thermo Fisher Scientific

Insights into protein function only cryo-EM can provide

The award-winning Thermo Scientific Krios G4 Cryo-TEM is a 300 kV cryo-transmission electron microscope engineered to enable 3D visualization of proteins and molecular machines, their localization, and dynamics within the architecture of the biological cell for unmatched biological insights. See the examples below of how biological scientists have sought to unlock the mysteries of life -- aging, curing disease, and enhancing health using the Krios Cryo-TEM.

Exploring structure-function relationships with cryo-ET

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Atomic resolution single particle analysis

Using a Krios G4 Cryo-TEM equipped with a Thermo Scientific Selectris X Imaging Filter, structural biologists achieved record-breaking resolution results, featured on the cover of Nature and other recent articles from Science and Nature. Scientists from the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK, obtained a 1.2 ångström resolution structure of the iron-storing protein apoferritin. They also achieved a 1.7 ångström resolution of membrane protein (GABA receptor), with an even sharper resolution in key parts of the protein. This human membrane protein has target sites for general anesthetics, benzodiazepines, barbiturates, and neuroactive steroids, making it very relevant to structure-based drug discovery. In addition to the resolution leap, the Selectris technology can also significantly impact productivity. By having a better filter and camera, you can achieve a specific resolution with much less data.

Human respiratory syncytial virus F variant

Structure of Human respiratory syncytial virus (RSV) F variant (construct pXCS847A) as described by Che et al. (PDB ID: 7UJA). The very first vaccine by GlaxoSmithKline (GSK) was approved by the Food and Drug Administration in 2023.

Janus Kinase (JAK) dimer

Structure of active Janus Kinase (JAK) dimer complexed with cytokine receptor intracellular domain as described by Glassman et al. (PDB ID: 7T6F). JAK is an essential component of cytokine signaling. Mutations to this kinase have led to immunodeficiency and myeloproliferative disorders.

SARS-CoV-2 Spike protein

Structural biology with cryo-EM has contributed to our understanding of SARS-CoV-2 since the beginning of the COVID-19 pandemic, providing critical information on the viral spike protein. Structure as described by Zhang et al. (PDB ID: 7KRQ).

TMEM106B filaments

Alzheimer’s disease associated TMEM106B filaments as described by Chang et al. (PDB ID: 7QVC). They showed that a previously unsolved amyloid fibril is composed of TMEM106B, a transmembrane lysosomal/endosomal protein.

Cellular cryo-tomography

The Krios G4 Cryo-TEM offers best in class cryo-electron tomography (cryo-ET) capabilities, providing nanometer-scale imaging of a cell’s interior in 3D and the visualization of protein complexes within their physiological environments. Using the Krios Cryo-TEM, tomography data can be obtained from whole bacterial cells or lamellae prepared with Thermo Scientific Aquilos, Arctis or Hydra Bio focused ion beam (Cryo-FIB) instruments.

Excitatory synapse of hippocampal neuron

Post-synaptic structure-like PSD filaments and glutamate receptors are clearly depicted as well as pre-synaptic structures such as vesicles or adhesion proteins. Courtesy of Guoqiang Bi oand Hong Zhou of UCLA.