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Atomic Structure of Human Adenovirus by Cryo-EM Reveals Interactions Among Protein Networks

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TLDR
The structure of the whole human adenovirus virion is reported at 3.6 angstroms resolution by cryo–electron microscopy (cryo-EM), revealing in situ atomic models of three minor capsid proteins, extensions of the major capsids, and interactions within three protein-protein networks.
Abstract
Construction of a complex virus may involve a hierarchy of assembly elements. Here, we report the structure of the whole human adenovirus virion at 3.6 angstroms resolution by cryo–electron microscopy (cryo-EM), revealing in situ atomic models of three minor capsid proteins (IIIa, VIII, and IX), extensions of the (penton base and hexon) major capsid proteins, and interactions within three protein-protein networks. One network is mediated by protein IIIa at the vertices, within group-of-six (GOS) tiles—a penton base and its five surrounding hexons. Another is mediated by ropes (protein IX) that lash hexons together to form group-of-nine (GON) tiles and bind GONs to GONs. The third, mediated by IIIa and VIII, binds each GOS to five surrounding GONs. Optimization of adenovirus for cancer and gene therapy could target these networks.

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RELION: implementation of a Bayesian approach to cryo-EM structure determination.

TL;DR: Developments that reduce the computational costs of the underlying maximum a posteriori (MAP) algorithm, as well as statistical considerations that yield new insights into the accuracy with which the relative orientations of individual particles may be determined are described.
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Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment

TL;DR: The formation of the protein corona, its structure and composition, and its influence on the physiological response are discussed, and an 'adsorbome' of 125 plasma proteins that are known to associate with nanomaterials are presented.
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How cryo-EM is revolutionizing structural biology

TL;DR: The recent advances in electron detection and image processing are reviewed and the exciting new opportunities that they offer to structural biology research are illustrated.
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2.2 Å resolution cryo-EM structure of β-galactosidase in complex with a cell-permeant inhibitor

TL;DR: The structure of a complex between Escherichia coli β-galactosidase and the cell-permeant inhibitor phenylethyl β-d-thiogalactopyranoside is determined by cryo-EM at an average resolution of ~2.2 angstroms, demonstrating that preparation of specimens of adequate quality and intrinsic protein flexibility now represent the major bottlenecks to routinely achieving resolutions close to 2 Å using single-particle cryo
References
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Journal ArticleDOI

Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy.

TL;DR: The hand determination and refinement optimization procedure is applied to image pairs of the dihydrolipoyl acetyltransferase (E2) catalytic core of the pyruvate dehydrogenase complex from Bacillus stearothermophilus taken by low-dose electron cryomicroscopy.
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Adenoviruses as Vaccine Vectors

TL;DR: The molecular biology of adenoviruses as well as ways the adanovirus vectors can be manipulated to enhance their efficacy as vaccine carriers are described and methods of evaluating immune responses to transgene products expressed byadenoviral vectors are described.
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Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity

TL;DR: Recombinant, replication-incompetent adenovirus serotype 5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens have proved highly immunogenic in preclinical studies but will probably be limited by the high prevalence of pre-existing anti-Ad5 immunity in human populations, particularly in the developing world.
Journal ArticleDOI

Adenovirus Protein VI Mediates Membrane Disruption following Capsid Disassembly

TL;DR: A new model of Ad entry is proposed based on the present observations of capsid disassembly and membrane penetration, which possessed membrane lytic activity similar to partially disassembled virions.
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