Structure Determination of Echovirus 1

Filman, David J.; Wien, M.W.; Cunningham, John J.; Bergelson, Jeffrey M.; Hogle, James M.

doi:10.1107/s0907444998002790

Cited by 52 publications

(40 citation statements)

References 13 publications

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“…The RMSD for the superimposition of C␣ atoms from 751 structurally equivalent residues in the two viruses is only 0.41 Å . A high structural similarity was also found between SVDV and CVA9 (22) or echovirus 1 (15), with RMSD values of only 0.57 and 0.59 Å , respectively, matching 751 residues in both superimpositions. Structural similarity is lower between SVDV and other enteroviruses such as poliovirus (14), with a RMSD for the C␣ atoms from the ␤-sandwiches of 0.98 Å .…”

Section: Vol 77 2003 Structure Of Swine Vesicular Disease Virus 9781mentioning

confidence: 92%

Structure of Swine Vesicular Disease Virus: Mapping of Changes Occurring during Adaptation of Human Coxsackie B5 Virus To Infect Swine

Verdaguer

Jiménez‐Clavero

Fita

et al. 2003

J Virol

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The structure of swine vesicular disease virus (SVDV) was solved and refined at a 3.0-Å resolution by X-ray crystallography to gain information about the role of sequence changes that occurred as this virus evolved from the parental human pathogen coxsackievirus B5 (CVB5). These amino acid substitutions can be clustered in five distinct regions: (i) the antigenic sites, (ii) the hydrophobic pocket of the VP1 ␤-sandwich, (iii) the putative CAR binding site, (iv) the putative heparan sulfate binding site, and (v) the fivefold axis. The VP1 pocket is occupied by a branched pocket factor, apparently different from that present in the closely related virus CVB3 and in other picornaviruses. This finding may be relevant for the design of new antiviral compounds against this site. Density consistent with the presence of ions was observed on the fivefold and threefold axes. The structure also provided an accurate description of the putative receptor binding sites.

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Section: Vol 77 2003 Structure Of Swine Vesicular Disease Virus 9781mentioning

confidence: 92%

Structure of Swine Vesicular Disease Virus: Mapping of Changes Occurring during Adaptation of Human Coxsackie B5 Virus To Infect Swine

Verdaguer

Jiménez‐Clavero

Fita

et al. 2003

J Virol

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“…Residues implicated in the previous study (25) (residues 199 -201, 212, 214, and 216) and in this study (Asn 289 ) are shown. It has been hypothesized that the ␣ 2 integrin I domain may bind to echovirus 1 within depressions that exist on the viral surface at both the 5-and 2-fold symmetry axes (25,26). The topography of these depressions may explain how residues that are quite distant from each other on the I domain, such as Asn…”

Section: Discussionmentioning

confidence: 99%

Determinants of Ligand Binding Specificity of the α1β1 and α2β1Integrins

Dickeson¹,

Mathis²,

Rahman³

et al. 1999

Journal of Biological Chemistry

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The ␣ 1 ␤ 1 and ␣ 2 ␤ 1 integrins are cell surface collagen receptors. Cells expressing the ␣ 1 ␤ 1 integrin preferentially adhere to collagen IV, whereas cells expressing the ␣ 2 ␤ 1 integrin preferentially adhere to collagen I. Recombinant ␣ 1 and ␣ 2 integrin I domains exhibit the same collagen type preferences as the intact integrins. In addition, the ␣ 2 integrin I domain binds echovirus 1; the ␣ 1 I domain does not. To identify the structural components of the I domains responsible for the varying ligand specificities, we have engineered several ␣ 1 /␣ 2 integrin I domain chimeras and evaluated their virus and collagen binding activities. Initially, large secondary structural components of the ␣ 2 I domain were replaced with corresponding regions of the ␣ 1 I domain. Following analysis in echovirus 1 and collagen binding assays, chimeras with successively smaller regions of ␣ 1 I were constructed and analyzed. The chimeras were analyzed by ELISA with several different ␣ 2 integrin monoclonal antibodies to assess their proper folding. Three different regions of the ␣ 1 I domain, when present in the ␣ 2 I domain, conferred enhanced collagen IV binding activity upon the ␣ 2 I domain. These include the ␣3 and ␣5 helices and a portion of the ␣6 helix. Echovirus 1 binding was lost in a chimera containing the ␣C-␣6 loop; higher resolution mapping identified Asn 289 as playing a critical role in echovirus 1 binding. Asn 289 had not been implicated in previous echovirus 1 binding studies. Taken together, these data reveal the existence of multiple determinants of ligand binding specificities within the ␣ 1 and ␣ 2 integrin I domains.The integrins constitute a large family of cell adhesion molecules that are involved in both cell-cell adhesion as well as the adhesion of cells to the extracellular matrix (for review see Ref. 1). The integrins are involved in many important physiologic processes including development and differentiation, cell migration, wound healing, thrombosis and hemostasis, metastasis, and immune system function. Structurally, integrins are heterodimeric glycoproteins composed of two noncovalently associated integral membrane subunits. The ␣ subunits range in size from 120 to 180 kDa, and the ␤ subunits range in size from 90 to 110 kDa. Many integrin subunits associate with more than a single ␣ or ␤ subunit resulting in a large number of different integrins.The ␤ 1 integrin subunit associates with at least 11 different ␣ subunits. Members of the resulting ␤ 1 subfamily of integrins are cell surface receptors for specific components of the extracellular matrix. The ␣ 1 ␤ 1 integrin is a cell surface receptor for several different collagens and laminin-1 (2). ␣ 1 ␤ 1 integrin-dependent adhesion of cells to collagens or laminin requires the presence of divalent cations (3). Similarly, the ␣ 2 ␤ 1 integrin also serves as a cell surface receptor for collagens and laminins (for review see Ref. 4), and the adhesion of cells via the ␣ 2 ␤ 1 integrin to these ligands also depends upon the presence of dival...

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“…We mapped the close contacts that the PALTAVETGHT motif has with the other capsid proteins (connected Van der Waals surfaces) and found that there are several contact points that are identical in all known enterovirus structures (10,11,14,15,19,24,29), and these are mostly conserved in rhinoviruses as well (3,13,18,31). In CAV9, these contact points are at the following positions: VP1/Leu31-VP3/Gln161, VP1/Leu31-VP3/Ser163, VP1/ Thr32-VP3/Ser163, VP1/Glu35-VP3/Ser162, VP1/Gly37-VP2/ His187, and VP1/Thr39-VP4/Thr54 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Coxsackievirus A9 VP1 Mutants with Enhanced or Hindered A Particle Formation and Decreased Infectivity

Airaksinen

Roivainen

Hovi

2001

J Virol

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We have studied coxsackievirus A9 (CAV9) mutants that each have a single amino acid substitution in the conserved 29-PALTAVETGHT-39 motif of VP1 and a reduced capacity to produce infectious progeny virus. After uncoating, all steps in the infection cycle occurred according to the same kinetics as and similar efficiency to the wild-type virus. However, the particle/infectious unit ratio in the progeny was significantly increased. The differences were apparently due to altered stability of the capsid: there were mutant viruses with enhanced or hindered uncoating, and both of these characteristics were found to reduce fitness under standard passaging conditions. At 32°C the instable mutants had an advantage, while the wild-type and the most stable mutant grew poorly. When comparing the newly published CAV9 structure and the other enterovirus structures, we found that the PALTAVETGHT motif is always in exactly the same position, in a cavity formed by the 3 other capsid proteins, with the C terminus of VP4 between this motif and the RNA. In the 7 enterovirus structures determined to date, the most conserved residues of the studied motif have identical contacts to neighboring residues of VP2, VP3, and VP4. We conclude that (i) the mutations affect the uncoating step necessary for infection, resulting in an untimely or hindered externalization of the VP1 N terminus together with the VP4, and (ii) the reason for the studied motif being evolutionarily conserved is its role in maintaining an optimal balance between the protective stability and the functional flexibility of the capsid.Coxsackievirus A9 (CAV9) is a member of the Enterovirus genus in the family Picornaviridae. Enteroviruses have icosahedral capsids that consist of 60 copies of each of the four capsid proteins VP1 to VP4. Their genomes are single molecules of positive-stranded RNA, approximately 7,500 nucleotides in length.In order to initiate a new infection cycle, enteroviruses have to attach to the host cell, uncoat to reveal the RNA, and at least the RNA must cross a membrane to enter the cell cytoplasm. For CAV9 there are at least two alternative receptors, the integrin ␣ v ␤ 3 (25,27), and an unidentified cell surface receptor (17,28). Several other specific receptors are known for various enteroviruses, but the mechanism and location of crossing the membrane are still unclear. It is known that the A particles, altered virus particles lacking the VP4 and having the N terminus of VP1 externalized, of poliovirus type 1 (PV1) are capable of binding to liposomes through the N terminus of VP1 (12). Furthermore, A particles as well as native polioviruses induce channel formation in an artificial membrane (30). The N terminus of VP1 might thus form a pore structure in one of the cell membranes, possibly together with VP4, allowing the RNA to be externalized from the capsid and enter the cytoplasm (12). The pseudoatomic models of the poliovirus 135S and 80S particles were recently determined by cryo-electron microscopy and image reconstruction (5). Based on the...

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Structure Determination of Echovirus 1

Cited by 52 publications

References 13 publications

Structure of Swine Vesicular Disease Virus: Mapping of Changes Occurring during Adaptation of Human Coxsackie B5 Virus To Infect Swine

Structure of Swine Vesicular Disease Virus: Mapping of Changes Occurring during Adaptation of Human Coxsackie B5 Virus To Infect Swine

Determinants of Ligand Binding Specificity of the α1β1 and α2β1Integrins

Coxsackievirus A9 VP1 Mutants with Enhanced or Hindered A Particle Formation and Decreased Infectivity

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