Breaking the next Cryo-EM resolution barrier – Atomic resolution determination of proteins!
Single particle cryo-EM is a powerful method to solve the three-dimensional structures of biological macromolecules. The technological development of electron microscopes, detectors, automated procedures in combination with user friendly image processing software and ever-increasing computational power have made cryo-EM a successful and largely expanding technology over the last decade. At resolutions better than 4 Å, atomic model building starts becoming possible but the direct visualization of true atomic positions in protein structure determination requires significantly higher (< 1.5 Å) resolution, which so far could not be attained by cryo-EM. The direct visualization of atom positions is essential for understanding protein-catalyzed chemical reaction mechanisms and to study drug-binding and -interference with protein function. In a new bioRxiv paper, Holger Stark et a. report a 1.25 Å resolution structure of apoferritin obtained by cryo-EM with a newly developed electron microscope providing unprecedented structural details. Their apoferritin structure has almost twice the 3D information content of the current world record reconstruction (at 1.54 Å resolution). For the first time in cryo-EM they can visualize individual atoms in a protein, see density for hydrogen atoms and single atom chemical modifications. Beyond the nominal improvement in resolution they can also show a significant improvement in quality of the cryo-EM density map which is highly relevant for using cryo-EM in structure-based drug design.
Upgrade of the workflow for cryo-electron tomography and microscopy
The CIISB Cryo-electron microscopy core facility at CEITEC Masaryk University is expanding its services in the sample preparation for electron microscopy. The facility has recently acquired high-pressure freezer Leica EM ICE for vitrification of bulky biological specimen (up to 200 mm thickness). In addition, the freeze-substitution unit Leica EM AFS2 for resin embedding of the high-pressure frozen samples and the ultramicrotom Leica EM UC7 with the adapter for cryo-ultramicrotomy were purchased in order to provide the facility users with the complete workflow for preparation of thin section samples for both room-temperature electron microscopy and cryo-electron microscopy.
Emerging Topics in Biomolecular Magnetic Resonance – Nick Cox & Kendra Frederick
The series Emerging topics in Biomolecular Magnetic Resonance will continue on July 9th at 16:00 CEST with the following lecturers and topics:
Nick Cox (Australian National University): Spin state evolution during the biological water splitting reaction
Kendra Frederick (UT Southwestern): In cell structural biology enabled by DNP MAS NMR
Emerging Topics in Biomolecular Magnetic Resonance – 4th edition
The series Emerging topics in Biomolecular Magnetic Resonance will continue on June 25th at 16:00 CEST with the following lecturers and topics:
Melinda J. Duer (University of Cambridge): Understanding extracellular matrix disease states with solid-state NMR?
Claudio Luchinat (University of Florence): NMR for metabolomics: again the ‘second best’ technique?
Emerging Topics in Biomolecular Magnetic Resonance – 3rd edition
The series Emerging topics in Biomolecular Magnetic Resonance will continue on June 18th at 16:00 CEST with the following lecturers and topics:
Tuo Wang (Louisiana State University): Elucidation of carbohydrate structure in plant biomass and fungal pathogens using solid-state NMR and DNP methods
Rina Rosenzweig (Weizmann Institute of Science): Molecular Chaperones in Protein Disaggregation - What we can learn from NMR