scholarly journals The Adenovirus Dodecahedron: Beyond the Platonic Story

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 718
Author(s):  
Solène Besson ◽  
Charles Vragniau ◽  
Emilie Vassal-Stermann ◽  
Marie Claire Dagher ◽  
Pascal Fender
Keyword(s):  
Electron Microscopy ◽  
Viral Entry ◽  
Physiological Role ◽  
Human Adenovirus ◽  
Structural Determinants ◽  
Cryo Electron Microscopy ◽  
Therapeutic Development ◽  
Adenovirus Receptor ◽  
Adenovirus Replication ◽  
Potential Use

Many geometric forms are found in nature, some of them adhering to mathematical laws or amazing aesthetic rules. One of the best-known examples in microbiology is the icosahedral shape of certain viruses with 20 triangular facets and 12 edges. What is less known, however, is that a complementary object displaying 12 faces and 20 edges called a ‘dodecahedron’ can be produced in huge amounts during certain adenovirus replication cycles. The decahedron was first described more than 50 years ago in the human adenovirus (HAdV3) viral cycle. Later on, the expression of this recombinant scaffold, combined with improvements in cryo-electron microscopy, made it possible to decipher the structural determinants underlying their architecture. Recently, this particle, which mimics viral entry, was used to fish the long elusive adenovirus receptor, desmoglein-2, which serves as a cellular docking for some adenovirus serotypes. This breakthrough enabled the understanding of the physiological role played by the dodecahedral particles, showing that icosahedral and dodecahedral particles live more than a simple platonic story. All these points are developed in this review, and the potential use of the dodecahedron in therapeutic development is discussed.

Structural Determinants of Rotavirus Subgroup Specificity Mapped by Cryo-electron Microscopy

2006 ◽  
Vol 356 (1) ◽  
pp. 209-221 ◽  
Author(s):  
Sarah L. Greig ◽  
John A. Berriman ◽  
Judith A. O'Brien ◽  
John A. Taylor ◽  
A. Richard Bellamy ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Structural Determinants ◽  
Cryo Electron Microscopy

The potential of cryo-electron microscopy for structure-based drug design

2017 ◽  
Vol 61 (5) ◽  
pp. 543-560 ◽  
Author(s):  
Andreas Boland ◽  
Leifu Chang ◽  
David Barford
Keyword(s):  
Electron Microscopy ◽  
Drug Discovery ◽  
Drug Design ◽  
Structural Information ◽  
Biological Molecules ◽  
Ligand Complex ◽  
Structure Based Drug Design ◽  
Technical Developments ◽  
Cryo Electron Microscopy ◽  
Therapeutic Development

Structure-based drug design plays a central role in therapeutic development. Until recently, protein crystallography and NMR have dominated experimental approaches to obtain structural information of biological molecules. However, in recent years rapid technical developments in single particle cryo-electron microscopy (cryo-EM) have enabled the determination to near-atomic resolution of macromolecules ranging from large multi-subunit molecular machines to proteins as small as 64 kDa. These advances have revolutionized structural biology by hugely expanding both the range of macromolecules whose structures can be determined, and by providing a description of macromolecular dynamics. Cryo-EM is now poised to similarly transform the discipline of structure-based drug discovery. This article reviews the potential of cryo-EM for drug discovery with reference to protein ligand complex structures determined using this technique.

scholarly journals The structure of enteric human adenovirus 41—A leading cause of diarrhea in children

2021 ◽  
Vol 7 (2) ◽  
pp. eabe0974
Author(s):  
K. Rafie ◽  
A. Lenman ◽  
J. Fuchs ◽  
A. Rajan ◽  
N. Arnberg ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Conformational Changes ◽  
Core Protein ◽  
Human Adenovirus ◽  
Structural Basis ◽  
Tissue Tropism ◽  
Penton Base ◽  
Viral Dna ◽  
Cryo Electron Microscopy ◽  
Protein Ix

Human adenovirus (HAdV) types F40 and F41 are a prominent cause of diarrhea and diarrhea-associated mortality in young children worldwide. These enteric HAdVs differ notably in tissue tropism and pathogenicity from respiratory and ocular adenoviruses, but the structural basis for this divergence has been unknown. Here, we present the first structure of an enteric HAdV—HAdV-F41—determined by cryo–electron microscopy to a resolution of 3.8 Å. The structure reveals extensive alterations to the virion exterior as compared to nonenteric HAdVs, including a unique arrangement of capsid protein IX. The structure also provides new insights into conserved aspects of HAdV architecture such as a proposed location of core protein V, which links the viral DNA to the capsid, and assembly-induced conformational changes in the penton base protein. Our findings provide the structural basis for adaptation of enteric HAdVs to a fundamentally different tissue tropism.

scholarly journals Five of Five VHHs Neutralizing Poliovirus Bind the Receptor-Binding Site

2016 ◽  
Vol 90 (7) ◽  
pp. 3496-3505 ◽  
Author(s):  
Mike Strauss ◽  
Lise Schotte ◽  
Bert Thys ◽  
David J. Filman ◽  
James M. Hogle
Keyword(s):  
Electron Microscopy ◽  
Quality Control ◽  
Binding Site ◽  
Receptor Binding ◽  
Viral Entry ◽  
Early Stage ◽  
Antiviral Agents ◽  
Receptor Binding Site ◽  
Cryo Electron Microscopy

ABSTRACTNanobodies, or VHHs, that recognize poliovirus type 1 have previously been selected and characterized as candidates for antiviral agents or reagents for standardization of vaccine quality control. In this study, we present high-resolution cryo-electron microscopy reconstructions of poliovirus with five neutralizing VHHs. All VHHs bind the capsid in the canyon at sites that extensively overlap the poliovirus receptor-binding site. In contrast, the interaction involves a unique (and surprisingly extensive) surface for each of the five VHHs. Five regions of the capsid were found to participate in binding with all five VHHs. Four of these five regions are known to alter during the expansion of the capsid associated with viral entry. Interestingly, binding of one of the VHHs, PVSS21E, resulted in significant changes of the capsid structure and thus seems to trap the virus in an early stage of expansion.IMPORTANCEWe describe the cryo-electron microscopy structures of complexes of five neutralizing VHHs with the Mahoney strain of type 1 poliovirus at resolutions ranging from 3.8 to 6.3Å. All five VHHs bind deep in the virus canyon at similar sites that overlap extensively with the binding site for the receptor (CD155). The binding surfaces on the VHHs are surprisingly extensive, but despite the use of similar binding surfaces on the virus, the binding surface on the VHHs is unique for each VHH. In four of the five complexes, the virus remains essentially unchanged, but for the fifth there are significant changes reminiscent of but smaller in magnitude than the changes associated with cell entry, suggesting that this VHH traps the virus in a previously undescribed early intermediate state. The neutralizing mechanisms of the VHHs and their potential use as quality control agents for the end game of poliovirus eradication are discussed.

scholarly journals Structural determinants of microtubule minus end preference in CAMSAP CKK domains

2019 ◽  
Author(s):  
Joseph Atherton ◽  
Yanzhang Luo ◽  
Shengqi Xiang ◽  
Chao Yang ◽  
Kai Jiang ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Polymer Structure ◽  
Protein Fold ◽  
Structural Determinants ◽  
Interaction Site ◽  
Cryo Electron Microscopy ◽  
Naegleria Gruberi

AbstractCAMSAP/Patronins regulate microtubule minus-end dynamics. Their end specificity is mediated by their CKK domains, which we proposed recognise specific tubulin conformations found at minus ends. To critically test this idea, we compared the human CAMSAP1 CKK domain (HsCKK) with a CKK domain fromNaegleria gruberi(NgCKK), which has lost minus-end specificity. Near-atomic cryo-electron microscopy structures of HsCKK- and NgCKK-microtubule complexes show that these CKK domains share the same protein fold, bind at the intradimer interprotofilament tubulin junction, but exhibit subtly different footprints on microtubules. Whereas NgCKK binding does not alter the microtubule architecture, HsCKK remodels its microtubule interaction site and changes the underlying polymer structure because the tubulin lattice conformation is not optimal for its binding. NMR experiments show that HsCKK is remarkably rigid, supporting this remodelling ability. Thus, in contrast to many MAPs, CKK domains can differentiate subtly specific tubulin conformations to enable microtubule minus-end recognition.

scholarly journals Cryo-EM structure of adenovirus type 3 fibre with desmoglein 2 shows a novel mode of receptor engagement

2018 ◽  
Author(s):  
Emilie Vassal-Stermann ◽  
Gregory Effantin ◽  
Chloe Zubieta ◽  
Wim Burmeister ◽  
Frédéric Iseni ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Host Cell ◽  
Adenoviral Vector ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Adenovirus Infection ◽  
Critical Step ◽  
Cryo Electron Microscopy ◽  
Type 3

AbstractAttachment of adenovirus (HAd) to host cell is a critical step of infection. This work reports the cryo-electron microscopy (cryo-EM) structure of a non-symmetrical complex smaller than 100kDa formed by the trimeric human adenovirus of type 3 fibre knob (HAd3K) and human desmoglein 2 (DSG2). The structure reveals a unique stoichiometry, shedding light to new adenovirus infection strategies and providing new insights for adenoviral vector development.

scholarly journals Structural determinants of microtubule minus end preference in CAMSAP CKK domains

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Joseph Atherton ◽  
Yanzhang Luo ◽  
Shengqi Xiang ◽  
Chao Yang ◽  
Ankit Rai ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Polymer Structure ◽  
Protein Fold ◽  
Structural Determinants ◽  
Interaction Site ◽  
Cryo Electron Microscopy ◽  
Naegleria Gruberi

AbstractCAMSAP/Patronins regulate microtubule minus-end dynamics. Their end specificity is mediated by their CKK domains, which we proposed recognise specific tubulin conformations found at minus ends. To critically test this idea, we compared the human CAMSAP1 CKK domain (HsCKK) with a CKK domain from Naegleria gruberi (NgCKK), which lacks minus-end specificity. Here we report near-atomic cryo-electron microscopy structures of HsCKK- and NgCKK-microtubule complexes, which show that these CKK domains share the same protein fold, bind at the intradimer interprotofilament tubulin junction, but exhibit different footprints on microtubules. NMR experiments show that both HsCKK and NgCKK are remarkably rigid. However, whereas NgCKK binding does not alter the microtubule architecture, HsCKK remodels its microtubule interaction site and changes the underlying polymer structure because the tubulin lattice conformation is not optimal for its binding. Thus, in contrast to many MAPs, the HsCKK domain can differentiate subtly specific tubulin conformations to enable microtubule minus-end recognition.

scholarly journals Structures of Adenovirus Incomplete Particles Clarify Capsid Architecture and Show Maturation Changes of Packaging Protein L1 52/55k

2015 ◽  
Vol 89 (18) ◽  
pp. 9653-9664 ◽  
Author(s):  
Gabriela N. Condezo ◽  
Roberto Marabini ◽  
Silvia Ayora ◽  
José M. Carazo ◽  
Raúl Alba ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Human Adenovirus ◽  
Virus Genome ◽  
Proteolytic Processing ◽  
Coat Proteins ◽  
Human Pathogens ◽  
X Ray ◽  
Cryo Electron Microscopy ◽  
Capsid Shell ◽  
Light Particles

ABSTRACTAdenovirus is one of the most complex icosahedral, nonenveloped viruses. Even after its structure was solved at near-atomic resolution by both cryo-electron microscopy and X-ray crystallography, the location of minor coat proteins is still a subject of debate. The elaborated capsid architecture is the product of a correspondingly complex assembly process, about which many aspects remain unknown. Genome encapsidation involves the concerted action of five virus proteins, and proteolytic processing by the virus protease is needed to prime the virion for sequential uncoating. Protein L1 52/55k is required for packaging, and multiple cleavages by the maturation protease facilitate its release from the nascent virion. Light-density particles are routinely produced in adenovirus infections and are thought to represent assembly intermediates. Here, we present the molecular and structural characterization of two different types of human adenovirus light particles produced by a mutant with delayed packaging. We show that these particles lack core polypeptide V but do not lack the density corresponding to this protein in the X-ray structure, thereby adding support to the adenovirus cryo-electron microscopy model. The two types of light particles present different degrees of proteolytic processing. Their structures provide the first glimpse of the organization of L1 52/55k protein inside the capsid shell and of how this organization changes upon partial maturation. Immature, full-length L1 52/55k is poised beneath the vertices to engage the virus genome. Upon proteolytic processing, L1 52/55k disengages from the capsid shell, facilitating genome release during uncoating.IMPORTANCEAdenoviruses have been extensively characterized as experimental systems in molecular biology, as human pathogens, and as therapeutic vectors. However, a clear picture of many aspects of their basic biology is still lacking. Two of these aspects are the location of minor coat proteins in the capsid and the molecular details of capsid assembly. Here, we provide evidence supporting one of the two current models for capsid architecture. We also show for the first time the location of the packaging protein L1 52/55k in particles lacking the virus genome and how this location changes during maturation. Our results contribute to clarifying standing questions in adenovirus capsid architecture and provide new details on the role of L1 52/55k protein in assembly.

scholarly journals Structure, receptor recognition and antigenicity of the human coronavirus CCoV-HuPn-2018 spike glycoprotein

2021 ◽  
Author(s):  
M. Alejandra Tortorici ◽  
Alexandra C Walls ◽  
Anshu Joshi ◽  
Young-Jun Park ◽  
Rachel T Eguia ◽  
...  
Keyword(s):  
Viral Entry ◽  
Nucleotide Polymorphisms ◽  
Spike Glycoprotein ◽  
Human Coronavirus ◽  
Single Nucleotide ◽  
Zoonotic Pathogen ◽  
Cryo Electron Microscopy ◽  
Receptor Recognition ◽  
Therapeutic Development ◽  
Entry Receptor

The recent isolation of CCoV-HuPn-2018 from a child respiratory swab indicates that more coronaviruses are spilling over to humans than previously appreciated. Here, we determined cryo-electron microscopy structures of the CCoV-HuPn-2018 spike glycoprotein trimer in two distinct conformational states and identified that it binds canine, feline and porcine aminopeptidase N (APN encoded by ANPEP) orthologs which serve as entry receptors. Introduction of an oligosaccharide at position N739 of human APN renders cells susceptible to CCoV-HuPn-2018 spike-mediated entry, suggesting that single nucleotide polymorphisms could account for the detection of this virus in some individuals. Human polyclonal plasma antibodies elicited by HCoV-229E infection and a porcine coronavirus monoclonal antibody inhibit CCoV-HuPn-2018 S-mediated entry, indicating elicitation of cross-neutralizing activity among α-coronaviruses. These data provide a blueprint of the CCoV-HuPn-2018 infection machinery, unveil the viral entry receptor and pave the way for vaccine and therapeutic development targeting this zoonotic pathogen.

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