Single-Particle Cryo-EM at Crystallographic Resolution.

By Yifan Cheng. 2015

531 citations recorded by the source corpus.

Until only a few years ago, single-particle electron cryo-microscopy (cryo-EM) was usually not the first choice for many structural biologists due to its limited resolution in the range of nanometer to subnanometer. Now, this method rivals X-ray crystallography in terms of resolution and can be used to determine atomic structures of macromolecules that are either refractory to crystallization or difficult to crystallize in specific functional states. In this review, I discuss the recent breakthroughs in both hardware and software that transformed cryo-microscopy, enabling understanding of complex biomolecules and their functions at atomic level.

Subfields: Atomic and Molecular Physics, and Optics, Condensed Matter Physics, Structural Biology

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Citations in the corpus

DeepPicker: a Deep Learning Approach for Fully Automated Particle Picking in Cryo-EM (2016, background): “Recent advance of the single-particle electron cryo-microscopy (cryo-EM) technique has been revolutionizing the structural biology ﬁeld [1, 2, 3], and enabled protein complex structure determination at near-atomic resolution [4, 5, 6, 7].”
Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology (2017, background): “Recent improvement in single particle cryo electron microscopy (Cheng, 2015) may soon reveal the structure of the nanomachine that mediates neuroexocytosis, allowing one to understand the molecular consequences of the cleavage of SNAP-25 by BoNT/A and BoNT/C.”
A Primer to Single-Particle Cryo-Electron Microscopy (2015, unknown): “In parallel, the continually increasing computer power allows the use of increasingly sophisticated image processing algorithms, resulting in greatly improved and more reliable 3D density maps (see also Cheng, 2015, this issue).”
De Novo Modeling in Cryo-EM Density Maps with Pathwalking (2016, background): “While cryo-Electron Microscopy(cryo-EM) has traditionally been limited to low resolution [1], it is now possible to produce structures for large macromolecular complexes at better than 3 Å resolution [2] [3] [4] [5], largely due to technological advances in electron detector technology [6].”
Localized reconstruction of subunits from electron cryomicroscopy images of macromolecular complexes (2015, methodology): “First the structure of the macromolecular complex is solved using conventional 3D refinement (1), after which the locations of the”
Current approaches for automated model building into cryo-EM maps using Buccaneer with CCP-EM (2020, methodology): “However, in these EM cases the amplitudes are less accurate than those measured from X-ray diffraction (Cheng, 2015).”
Toward the solution of the protein structure prediction problem (2021, methodology): “Among the most accurate experimental methods for determining the structures of proteins are X-ray crystallography (10), NMR spectroscopy (11), and cryo-electron microscopy (12).”
Q|R: quantum-based refinement. (2017, background): “Cryo-electron microscopy (cryo-EM) is rapidly becoming its major competitor (Bai et al., 2015; Cheng, 2015).”
Accelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2 (2016, methodology): “With the advent of direct-electron detectors and advanced methods of image processing, structural characterisation of macromolecular complexes to near-atomic resolution is now feasible using single-particle electron cryo-microscopy (cryo-EM) ( Cheng, 2015 ; Fernandez-Leiro and Scheres, 2016b ).”