Abstract
Cryogenic transmission electron microscopy (cryo-TEM) is a high-resolution biological imaging method, whereby biological samples, such as purified proteins, macromolecular complexes, viral particles, organelles and cells, are embedded in vitreous ice preserving their native structures. Due to sensitivity of biological materials to the electron beam of the microscope, only relatively low electron doses can be applied during imaging. As a result, the signal arising from the structure of interest is overpowered by noise in the images. To increase the signal-to-noise ratio, different image processing-based strategies that aim at coherent averaging of signal have been devised. In such strategies, images are generally assumed to arise from multiple identical copies of the structure. Prior to averaging, the images must be grouped according to the view of the structure they represent and images representing the same view must be simultaneously aligned relatively to each other. For computational reconstruction of the 3D structure, images must contain different views of the original structure. Structures with multiple symmetry-related substructures are advantageous in averaging approaches because each image provides multiple views of the substructures. However, the symmetry assumption may be valid for only parts of the structure, leading to incoherent averaging of the other parts. Several image processing approaches have been adapted to tackle symmetry-mismatched substructures with increasing success. Such structures are ubiquitous in nature and further computational method development is needed to understanding their biological functions.
Highlights
Cryogenic transmission electron microscopy allows reconstructing 3D density maps of biological macromolecules from projection images of individual copies of the macromolecule, referred to as single particles [1]
If the site of the symmetry mismatch is at the five-fold symmetric vertex of an icosahedrally symmetric particle, we shall define this as ‘I-C5’. (For consistency, if no local symmetry is present at the binding site, we denote this with C1–vC1 density (C1).) we define the symmetry of the symmetry-mismatched substructure
By pseudo-symmetry (p), in contrast, we refer to structures that can be considered to be symmetric at low resolution, but this symmetry assumption breaks down at high resolution, for example if the amino acid sequences of the symmetry-related subunits are not identical (Figure 1d)
Summary
Image processing for cryogenic transmission electron microscopy of symmetry-mismatched complexes. To increase the signal-to-noise ratio, different image processing-based strategies that aim at coherent averaging of signal have been devised. In such strategies, images are generally assumed to arise from multiple identical copies of the structure. Structures with multiple symmetry-related substructures are advantageous in averaging approaches because each image provides multiple views of the substructures. Several image processing approaches have been adapted to tackle symmetry-mismatched substructures with increasing success. Such structures are ubiquitous in nature and further computational method development is needed to understanding their biological functions. Accepted Manuscript Online: 08 February 2018 Version of Record published: 16 March 2018
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