Structural and Functional Analysis of Murine Polyomavirus Capsid Proteins Establish the Determinants of Ligand Recognition and Pathogenicity
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{"title"=>"Structural and Functional Analysis of Murine Polyomavirus Capsid Proteins Establish the Determinants of Ligand Recognition and Pathogenicity", "type"=>"journal", "authors"=>[{"first_name"=>"Michael H.C.", "last_name"=>"Buch", "scopus_author_id"=>"25724085900"}, {"first_name"=>"A. Manuel", "last_name"=>"Liaci", "scopus_author_id"=>"56543767600"}, {"first_name"=>"Samantha D.", "last_name"=>"O’Hara", "scopus_author_id"=>"56940681500"}, {"first_name"=>"Robert L.", "last_name"=>"Garcea", "scopus_author_id"=>"7004407503"}, {"first_name"=>"Ursula", "last_name"=>"Neu", "scopus_author_id"=>"24076969800"}, {"first_name"=>"Thilo", "last_name"=>"Stehle", "scopus_author_id"=>"7003736109"}], "year"=>2015, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537374", "doi"=>"10.1371/journal.ppat.1005104", "sgr"=>"84946022161", "scopus"=>"2-s2.0-84946022161", "isbn"=>"1553-7374", "pmid"=>"26474293", "pui"=>"606741092"}, "id"=>"882fdb59-4127-391e-9e95-59a4bdc3f80b", "abstract"=>"Murine polyomavirus (MuPyV) causes tumors of various origins in newborn mice and hamsters. Infection is initiated by attachment of the virus to ganglioside receptors at the cell surface. Single amino acid exchanges in the receptor-binding pocket of the major capsid protein VP1 are known to drastically alter tumorigenicity and spread in closely related MuPyV strains. The virus represents a rare example of differential receptor recognition directly influencing viral pathogenicity, although the factors underlying these differences remain unclear. We performed structural and functional analyses of three MuPyV strains with strikingly different pathogenicities: the low-tumorigenicity strain RA, the high-pathogenicity strain PTA, and the rapidly growing, lethal laboratory isolate strain LID. Using ganglioside deficient mouse embryo fibroblasts, we show that addition of specific gangliosides restores infectability for all strains, and we uncover a complex relationship between virus attachment and infection. We identify a new infectious ganglioside receptor that carries an additional linear [α-2,8]-linked sialic acid. Crystal structures of all three strains complexed with representative oligosaccharides from the three main pathways of ganglioside biosynthesis provide the molecular basis of receptor recognition. All strains bind to a range of sialylated glycans featuring the central [α-2,3]-linked sialic acid present in the established receptors GD1a and GT1b, but the presence of additional sialic acids modulates binding. An extra [α-2,8]-linked sialic acid engages a protein pocket that is conserved among the three strains, while another, [α-2,6]-linked branching sialic acid lies near the strain-defining amino acids but can be accommodated by all strains. By comparing electron density of the oligosaccharides within the binding pockets at various concentrations, we show that the [α-2,8]-linked sialic acid increases the strength of binding. Moreover, the amino acid exchanges have subtle effects on their affinity for the validated receptor GD1a. Our results indicate that both receptor specificity and affinity influence MuPyV pathogenesis.", "link"=>"http://www.mendeley.com/research/structural-functional-analysis-murine-polyomavirus-capsid-proteins-establish-determinants-ligand-rec", "reader_count"=>23, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>3, "Researcher"=>3, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Bachelor"=>6}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>3, "Researcher"=>3, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Bachelor"=>6}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>6, "Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>2, "Chemistry"=>1, "Decision Sciences"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Chemistry"=>{"Chemistry"=>1}, "Decision Sciences"=>{"Decision Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>2, "France"=>1, "Germany"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2364062"], "description"=>"<p>The average simulated annealing F<sub>obs</sub>-F<sub>calc</sub> electron density for the Neu5Ac<sub>a</sub>-[α-2,3]-Gal<sub>a</sub> in GT1a, GD1a, and DSLNT is plotted against ligand concentration. RA VP1 is colored blue, PTA VP1, is colored red, and LID VP1 is colored green. GT1a is displayed in a dotted line with triangles, GD1a in a dashed line with circles, and DSLNT in a solid line with squares. The error bars correspond to the standard deviation of the mean electron density observed in the five chains of VP1. <b>A</b> Electron density of GT1a, GD1a, and DSLNT in RA VP1. <b>B</b> Same as in <b>A</b>, but for PTA VP1. <b>C</b> Same as in <b>A</b>, but for LID VP1. <b>D</b> Comparison of GT1a-derived electron density in RA VP1, PTA VP1, and LID VP1. <b>E</b> Same as in <b>D</b>, but for GD1a. <b>F</b> Same as in <b>D</b>, but for DSLNT.</p>", "links"=>[], "tags"=>["lid", "MuPyV strains", "ra", "Murine Polyomavirus Capsid Proteins", "gt", "sialic acid", "Pathogenicity Murine polyomavirus", "receptors GD 1a", "receptor recognition", "ganglioside", "sialic acids modulates binding", "sialic acid increases", "pta", "receptor GD 1a", "capsid protein VP 1", "sialic acid engages", "acid exchanges", "mouse embryo fibroblasts", "affinity influence MuPyV pathogenesis"], "article_id"=>1578816, "categories"=>["Biological Sciences"], "users"=>["Michael H. C. Buch", "A. Manuel Liaci", "Samantha D. O’Hara", "Robert L. Garcea", "Ursula Neu", "Thilo Stehle"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005104.g007", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Binding_of_ligands_to_MuPyV_VP1_/1578816", "title"=>"Binding of ligands to MuPyV VP1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 04:30:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364063"], "description"=>"<p>Description of the investigated MuPyV strains.</p>", "links"=>[], "tags"=>["lid", "MuPyV strains", "ra", "Murine Polyomavirus Capsid Proteins", "gt", "sialic acid", "Pathogenicity Murine polyomavirus", "receptors GD 1a", "receptor recognition", "ganglioside", "sialic acids modulates binding", "sialic acid increases", "pta", "receptor GD 1a", "capsid protein VP 1", "sialic acid engages", "acid exchanges", "mouse embryo fibroblasts", "affinity influence MuPyV pathogenesis"], "article_id"=>1578817, "categories"=>["Biological Sciences"], "users"=>["Michael H. C. Buch", "A. Manuel Liaci", "Samantha D. O’Hara", "Robert L. Garcea", "Ursula Neu", "Thilo Stehle"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005104.t001", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Description_of_the_investigated_MuPyV_strains_/1578817", "title"=>"Description of the investigated MuPyV strains.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-10-16 04:30:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364064"], "description"=>"<p>Data collection and refinement statistics.</p>", "links"=>[], "tags"=>["lid", "MuPyV strains", "ra", "Murine Polyomavirus Capsid Proteins", "gt", "sialic acid", "Pathogenicity Murine polyomavirus", "receptors GD 1a", "receptor recognition", "ganglioside", "sialic acids modulates binding", "sialic acid increases", "pta", "receptor GD 1a", "capsid protein VP 1", "sialic acid engages", "acid exchanges", "mouse embryo fibroblasts", "affinity influence MuPyV pathogenesis"], "article_id"=>1578818, "categories"=>["Biological Sciences"], "users"=>["Michael H. C. Buch", "A. Manuel Liaci", "Samantha D. O’Hara", "Robert L. Garcea", "Ursula Neu", "Thilo Stehle"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005104.t002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Data_collection_and_refinement_statistics_/1578818", "title"=>"Data collection and refinement statistics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-10-16 04:30:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364039"], "description"=>"<p>The glycan parts of important members are shown for each series. The downstream biosynthetic steps are identical for all members of a row, although they may vary in linkage orientation. The six-membered pyranose rings are numbered counterclockwise, starting from the bottom (C1, except for C2 in Neu5Ac), and the ring oxygen is symbolized with a black dot. Neu5Ac moieties are rearranged for clarity, and all linkages are mediated by O2 or O8. Most of the gangliosides (e.g. LM1) can be further modified, e.g. by fucosylation. Linkages involving Neu5Ac are present in the α conformation, all other linkages are in the β conformation. Boxes represent three distinguishable sialoglycotopes that contain linkages found in GT1a (blue, representative for [α-2,8]), GD1a (green, [α-2,3]), and 3’-6’-iso-LD1 (also referred to as DSLNT, orange, [α-2,6]). The naming is according to the corresponding gangliosides; if possible, the Svennerholm shorthand is used [<a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005104#ppat.1005104.ref064\" target=\"_blank\">64</a>–<a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005104#ppat.1005104.ref066\" target=\"_blank\">66</a>] All biosynthetic routes were verified using the KEGG metabolic pathway database [<a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005104#ppat.1005104.ref067\" target=\"_blank\">67</a>]. A prototype glycan that exemplifies the different positions of Gal and Neu5Ac moieties is depicted on the lower right. The glycan portions investigated in this study are highlighted by purple boxes.</p>", "links"=>[], "tags"=>["lid", "MuPyV strains", "ra", "Murine Polyomavirus Capsid Proteins", "gt", "sialic acid", "Pathogenicity Murine polyomavirus", "receptors GD 1a", "receptor recognition", "ganglioside", "sialic acids modulates binding", "sialic acid increases", "pta", "receptor GD 1a", "capsid protein VP 1", "sialic acid engages", "acid exchanges", "mouse embryo fibroblasts", "affinity influence MuPyV pathogenesis"], "article_id"=>1578801, "categories"=>["Biological Sciences"], "users"=>["Michael H. C. Buch", "A. Manuel Liaci", "Samantha D. O’Hara", "Robert L. Garcea", "Ursula Neu", "Thilo Stehle"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005104.g001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overview_and_biosynthetic_pathway_of_the_four_most_prominent_ganglioside_series_/1578801", "title"=>"Overview and biosynthetic pathway of the four most prominent ganglioside series.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 04:30:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364085", "https://ndownloader.figshare.com/files/2364086", "https://ndownloader.figshare.com/files/2364087", "https://ndownloader.figshare.com/files/2364088", "https://ndownloader.figshare.com/files/2364089", "https://ndownloader.figshare.com/files/2364090", "https://ndownloader.figshare.com/files/2364091", "https://ndownloader.figshare.com/files/2364092", "https://ndownloader.figshare.com/files/2364093"], "description"=>"<div><p>Murine polyomavirus (MuPyV) causes tumors of various origins in newborn mice and hamsters. Infection is initiated by attachment of the virus to ganglioside receptors at the cell surface. Single amino acid exchanges in the receptor-binding pocket of the major capsid protein VP1 are known to drastically alter tumorigenicity and spread in closely related MuPyV strains. The virus represents a rare example of differential receptor recognition directly influencing viral pathogenicity, although the factors underlying these differences remain unclear. We performed structural and functional analyses of three MuPyV strains with strikingly different pathogenicities: the low-tumorigenicity strain RA, the high-pathogenicity strain PTA, and the rapidly growing, lethal laboratory isolate strain LID. Using ganglioside deficient mouse embryo fibroblasts, we show that addition of specific gangliosides restores infectability for all strains, and we uncover a complex relationship between virus attachment and infection. We identify a new infectious ganglioside receptor that carries an additional linear [α-2,8]-linked sialic acid. Crystal structures of all three strains complexed with representative oligosaccharides from the three main pathways of ganglioside biosynthesis provide the molecular basis of receptor recognition. All strains bind to a range of sialylated glycans featuring the central [α-2,3]-linked sialic acid present in the established receptors GD1a and GT1b, but the presence of additional sialic acids modulates binding. An extra [α-2,8]-linked sialic acid engages a protein pocket that is conserved among the three strains, while another, [α-2,6]-linked branching sialic acid lies near the strain-defining amino acids but can be accommodated by all strains. By comparing electron density of the oligosaccharides within the binding pockets at various concentrations, we show that the [α-2,8]-linked sialic acid increases the strength of binding. Moreover, the amino acid exchanges have subtle effects on their affinity for the validated receptor GD1a. Our results indicate that both receptor specificity and affinity influence MuPyV pathogenesis.</p></div>", "links"=>[], "tags"=>["lid", "MuPyV strains", "ra", "Murine Polyomavirus Capsid Proteins", "gt", "sialic acid", "Pathogenicity Murine polyomavirus", "receptors GD 1a", "receptor recognition", "ganglioside", "sialic acids modulates binding", "sialic acid increases", "pta", "receptor GD 1a", "capsid protein VP 1", "sialic acid engages", "acid exchanges", "mouse embryo fibroblasts", "affinity influence MuPyV pathogenesis"], "article_id"=>1578834, "categories"=>["Biological Sciences"], "users"=>["Michael H. C. Buch", "A. Manuel Liaci", "Samantha D. O’Hara", "Robert L. Garcea", "Ursula Neu", "Thilo Stehle"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005104.s001", "https://dx.doi.org/10.1371/journal.ppat.1005104.s002", "https://dx.doi.org/10.1371/journal.ppat.1005104.s003", "https://dx.doi.org/10.1371/journal.ppat.1005104.s004", "https://dx.doi.org/10.1371/journal.ppat.1005104.s005", "https://dx.doi.org/10.1371/journal.ppat.1005104.s006", "https://dx.doi.org/10.1371/journal.ppat.1005104.s007", "https://dx.doi.org/10.1371/journal.ppat.1005104.s008", "https://dx.doi.org/10.1371/journal.ppat.1005104.s009"], "stats"=>{"downloads"=>6, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Structural_and_Functional_Analysis_of_Murine_Polyomavirus_Capsid_Proteins_Establish_the_Determinants_of_Ligand_Recognition_and_Pathogenicity_/1578834", "title"=>"Structural and Functional Analysis of Murine Polyomavirus Capsid Proteins Establish the Determinants of Ligand Recognition and Pathogenicity", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-10-16 04:30:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364041"], "description"=>"<p>Ganglioside knock-out (Gang-/-) MEFs were completely resistant to infection of all strains of MuPyV as shown by the absence of T-antigen positive nuclei at 24 hours post infection (DMSO control). GD1a, GT1b, and GT1a ganglioside supplementation of Gang-/- MEFs restored RA (<b>A</b>), PTA (<b>B</b>), and LID MuPyV (<b>C</b>) infection, while GD1b and GM1 supplementation resulted in little to no infection by any virus strain. Infection levels were quantified at both 2 μM and 4 μM ganglioside supplementation (blue and green bars, respectively). Infection levels are normalized to MuPyV infection of WT MEFs, and error bars correspond to standard error.</p>", "links"=>[], "tags"=>["lid", "MuPyV strains", "ra", "Murine Polyomavirus Capsid Proteins", "gt", "sialic acid", "Pathogenicity Murine polyomavirus", "receptors GD 1a", "receptor recognition", "ganglioside", "sialic acids modulates binding", "sialic acid increases", "pta", "receptor GD 1a", "capsid protein VP 1", "sialic acid engages", "acid exchanges", "mouse embryo fibroblasts", "affinity influence MuPyV pathogenesis"], "article_id"=>1578803, "categories"=>["Biological Sciences"], "users"=>["Michael H. C. Buch", "A. Manuel Liaci", "Samantha D. O’Hara", "Robert L. Garcea", "Ursula Neu", "Thilo Stehle"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005104.g002", "stats"=>{"downloads"=>1, "page_views"=>39, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GT1a_GT1b_and_GD1a_supplementation_rescues_MuPyV_infection_of_Gang_MEFs_/1578803", "title"=>"GT1a, GT1b, and GD1a supplementation rescues MuPyV infection of Gang-/- MEFs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 04:30:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364044"], "description"=>"<p>Top view on the receptor-binding region of PTA, which is shown with E91 and V296 highlighted in salmon. Residues that are known to participate in receptor binding are contributed by the BC and HI loops and are highlighted as stick models. One monomer is shaded in green and the other monomers are alternatingly shaded light and dark grey for better distinction.</p>", "links"=>[], "tags"=>["lid", "MuPyV strains", "ra", "Murine Polyomavirus Capsid Proteins", "gt", "sialic acid", "Pathogenicity Murine polyomavirus", "receptors GD 1a", "receptor recognition", "ganglioside", "sialic acids modulates binding", "sialic acid increases", "pta", "receptor GD 1a", "capsid protein VP 1", "sialic acid engages", "acid exchanges", "mouse embryo fibroblasts", "affinity influence MuPyV pathogenesis"], "article_id"=>1578806, "categories"=>["Biological Sciences"], "users"=>["Michael H. C. Buch", "A. Manuel Liaci", "Samantha D. O’Hara", "Robert L. Garcea", "Ursula Neu", "Thilo Stehle"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005104.g003", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_MuPyV_binding_pocket_/1578806", "title"=>"The MuPyV binding pocket.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 04:30:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364048"], "description"=>"<p><b>A</b> The PTA binding pocket and the GT1a conformation upon binding are shown from an angle parallel to the fivefold axis. A scheme of the glycan is shown in the inset, and the sugar rings are filled according to the coloring scheme from <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005104#ppat.1005104.g001\" target=\"_blank\">Fig 1</a>. <b>B</b> Simulated annealing F<sub>obs</sub>-F<sub>calc</sub> omit map (resolution 1.71 Å, calculated at 3.5 σ, carved 2.3 Å around the glycan). <b>C</b> Possible binding interactions of GT1a and PTA. E91 and V296 are highlighted in salmon. Hydrogen bonds are shown in black, the hydrophobic contact mediated by V296 in gold, and the van-der-Waals contacts of E91 are shown in cyan. Waters that mediate key hydrogen bonds are shown as red spheres. Unique interactions mediated by the novel GT1a-like binding motif are shown in red. <b>D</b> Zoomed view of the binding to the two terminal Neu5Ac moieties. The rest of the glycan is omitted for clarity. Residues except Y72 and R77 as well as waters involved in contacts with these two glycan moieties are pale grey and salmon, respectively.</p>", "links"=>[], "tags"=>["lid", "MuPyV strains", "ra", "Murine Polyomavirus Capsid Proteins", "gt", "sialic acid", "Pathogenicity Murine polyomavirus", "receptors GD 1a", "receptor recognition", "ganglioside", "sialic acids modulates binding", "sialic acid increases", "pta", "receptor GD 1a", "capsid protein VP 1", "sialic acid engages", "acid exchanges", "mouse embryo fibroblasts", "affinity influence MuPyV pathogenesis"], "article_id"=>1578810, "categories"=>["Biological Sciences"], "users"=>["Michael H. C. Buch", "A. Manuel Liaci", "Samantha D. O’Hara", "Robert L. Garcea", "Ursula Neu", "Thilo Stehle"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005104.g004", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Binding_of_GT1a_to_PTA_/1578810", "title"=>"Binding of GT1a to PTA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 04:30:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364049"], "description"=>"<p><b>A</b> Superposition of the GT1a-binding mode of RA (GT1a in sky blue), PTA (dark blue), and LID (pale blue). The Neu5Ac<sub>b</sub>-[α-2,8]-Neu5Ac<sub>a</sub>-[α-2,3]-Gal<sub>a</sub> motif is shown in solid sticks, together with the adjacent GalNAc moiety. All superpositionings were carried out in PyMOL [<a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005104#ppat.1005104.ref061\" target=\"_blank\">61</a>] using ‘align’ for the protein chains only. Surface, E91 and V296 are from PTA/GT1a. All ‘align’ rmsd values are below 0.16 Å. <b>B & C</b> Close view of the van-der-Waals contacts introduced by the E91 side chain present in PTA and LID (C), but not in RA (B). Hydrogen bonds are shown in grey, van-der-Waals contacts in cyan. <b>D & E</b> Close view of the hydrophobic contact mediated by V296 in RA and PTA (D), but not by A296 in LID (E). The 4.0 Å hydrophobic contact is not present in the LID strain, whose pocket is opened to the right. Hydrogen bonds are shown in grey, hydrophobic contacts are shown in gold.</p>", "links"=>[], "tags"=>["lid", "MuPyV strains", "ra", "Murine Polyomavirus Capsid Proteins", "gt", "sialic acid", "Pathogenicity Murine polyomavirus", "receptors GD 1a", "receptor recognition", "ganglioside", "sialic acids modulates binding", "sialic acid increases", "pta", "receptor GD 1a", "capsid protein VP 1", "sialic acid engages", "acid exchanges", "mouse embryo fibroblasts", "affinity influence MuPyV pathogenesis"], "article_id"=>1578811, "categories"=>["Biological Sciences"], "users"=>["Michael H. C. Buch", "A. Manuel Liaci", "Samantha D. O’Hara", "Robert L. Garcea", "Ursula Neu", "Thilo Stehle"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005104.g005", "stats"=>{"downloads"=>2, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Binding_modes_of_GT1a_to_the_different_MuPyV_strains_/1578811", "title"=>"Binding modes of GT1a to the different MuPyV strains.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 04:30:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2364061"], "description"=>"<p><b>A</b> Superposition of the binding modes of GD1a to RA (light green), PTA (dark green), and LID (pale green). The sequence of GD1a is shown in the inset. The Neu5Ac<sub>a</sub>-[α-2,3]-Gal<sub>a</sub> motif is shown in solid sticks, together with the adjacent GalNAc moiety. In all figures, GT1a bound to PTA is overlaid as a grey ghost for comparison, with Neu5Ac<sub>b</sub> omitted for clarity. Deviations exceeding the atomic error of the structure and alignment rmsd values are only found in the stem region of the sugar, starting at Gal<sub>b</sub>. All superpositionings were carried out in PyMOL [<a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005104#ppat.1005104.ref061\" target=\"_blank\">61</a>] using ‘align’ for the protein chains only. Surface, E91 and V296 are from PTA/GT1a. All ‘align’ rmsd values are below 0.16 Å. <b>B & C</b> Comparison of the DSLNT binding modes to RA (red), PTA (orange), and LID (violet). In PTA-DSLNT, [α-2,6]-branching causes a 15–20° psi angle shift of the GlcNAc moiety compared to GD1a and GT1a, resulting in a 1 Å sideward twist movement of the stem. In RA-DSLNT, combination of this shift with a 15° shift in the phi angle results in a downward movement of GlcNAc and its branching Neu5Ac<sub>c</sub> compared to PTA-DSLNT. In LID, the shift is already observable for Gal<sub>a</sub> and results in the loss of ordered density for GlcNAc. All angles were analyzed with CARP. The sequence of DSLNT is shown in the inset of panel C.</p>", "links"=>[], "tags"=>["lid", "MuPyV strains", "ra", "Murine Polyomavirus Capsid Proteins", "gt", "sialic acid", "Pathogenicity Murine polyomavirus", "receptors GD 1a", "receptor recognition", "ganglioside", "sialic acids modulates binding", "sialic acid increases", "pta", "receptor GD 1a", "capsid protein VP 1", "sialic acid engages", "acid exchanges", "mouse embryo fibroblasts", "affinity influence MuPyV pathogenesis"], "article_id"=>1578815, "categories"=>["Biological Sciences"], "users"=>["Michael H. C. Buch", "A. Manuel Liaci", "Samantha D. O’Hara", "Robert L. Garcea", "Ursula Neu", "Thilo Stehle"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005104.g006", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differences_in_receptor_binding_patterns_across_glycans_/1578815", "title"=>"Differences in receptor binding patterns across glycans.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 04:30:47"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"12", "full-text"=>"13", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"29", "full-text"=>"34", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"20", "full-text"=>"24", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"13", "full-text"=>"17", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"16", "full-text"=>"17", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"32", "full-text"=>"34", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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