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Open AccessJournal ArticleDOI

Adding the Third Dimension to Virus Life Cycles: Three-Dimensional Reconstruction of Icosahedral Viruses from Cryo-Electron Micrographs

TLDR
The success of cryo-electron microscopy in combination with three-dimensional image reconstruction for icosahedral viruses provides a firm foundation for future explorations of more-complex viral pathogens, including the vast number that are nonspherical or nonsymmetrical.
Abstract
Viruses are cellular parasites. The linkage between viral and host functions makes the study of a viral life cycle an important key to cellular functions. A deeper understanding of many aspects of viral life cycles has emerged from coordinated molecular and structural studies carried out with a wide range of viral pathogens. Structural studies of viruses by means of cryo-electron microscopy and three-dimensional image reconstruction methods have grown explosively in the last decade. Here we review the use of cryo-electron microscopy for the determination of the structures of a number of icosahedral viruses. These studies span more than 20 virus families. Representative examples illustrate the use of moderate- to low-resolution (7- to 35-A) structural analyses to illuminate functional aspects of viral life cycles including host recognition, viral attachment, entry, genome release, viral transcription, translation, proassembly, maturation, release, and transmission, as well as mechanisms of host defense. The success of cryo-electron microscopy in combination with three-dimensional image reconstruction for icosahedral viruses provides a firm foundation for future explorations of more-complex viral pathogens, including the vast number that are nonspherical or nonsymmetrical.

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Journal ArticleDOI

Structure of dengue virus: implications for flavivirus organization, maturation, and fusion.

TL;DR: The first structure of a flavivirus has been determined by using a combination of cryoelectron microscopy and fitting of the known structure of glycoprotein E into the electron density map, suggesting that flaviviruses employ a fusion mechanism in which the distal beta barrels of domain II of the glycop Protein E are inserted into the cellular membrane.
Journal ArticleDOI

Single-particle electron cryo-microscopy: towards atomic resolution.

TL;DR: Electron microscopy is a very direct method of structure determination that complements the well-established techniques of X-ray crystallography and NMR spectroscopy and is established itself as an important – still upcoming – technique for studying the structures of large biological macromolecules.
Journal ArticleDOI

Colloquium: Opportunities in nanomagnetism

TL;DR: Nanomagnetism is the discipline dealing with magnetic phenomena specific to structures having dimensions in the submicron range as discussed by the authors, and it shares many of the same basic organizing principles such as geometric confinement, physical proximity and chemical self-organization.
Journal ArticleDOI

Influenza virus pleiomorphy characterized by cryoelectron tomography.

TL;DR: Cryoelectron tomography is used to visualize the 3D structures of 110 individual virions of the X-31 (H3N2) strain of influenza A, and some virions have substantial gaps in their matrix layer, and others appear to lack a matrix layer entirely, suggesting the existence of an alternative budding pathway in which matrix protein is minimally involved.
Journal ArticleDOI

Structures of immature flavivirus particles

TL;DR: Structures of prM‐containing dengue and yellow fever virus particles were determined to 16 and 25 Å resolution by cryoelectron microscopy and image reconstruction techniques, consistent with the predicted membrane‐spanning domains of the unprocessed polyprotein.
References
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Journal ArticleDOI

Improved methods for building protein models in electron density maps and the location of errors in these models.

TL;DR: In this paper, the authors describe strategies and tools that help to alleviate this problem and simplify the model-building process, quantify the goodness of fit of the model on a per-residue basis and locate possible errors in peptide and side-chain conformations.
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Communication in the presence of noise

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Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy.

TL;DR: A complete atomic model for bacteriorhodopsin between amino acid residues 8 and 225 has been built and suggests that pK changes in the Schiff base must act as the means by which light energy is converted into proton pumping pressure in the channel.
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Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution.

TL;DR: The haemagglutinin glycoprotein of influenza virus is a trimer comprising two structurally distinct regions: a triple-stranded coiled-coil of α-helices extends 76 Å from the membrane and a globular region of antiparallel β-sheet is positioned on top of this stem.
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Physical Principles in the Construction of Regular Viruses

TL;DR: The authors' designs obey strict icosahedral symmetry, with the asymmetric unit in each case containing a heterodimer that comprises one subunit from each of the two components.
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