Galactose Recognition by the Apicomplexan Parasite Toxoplasma gondii

Marchant, Jan; Cowper, Ben; Liu, Yan; Lai, Livia; Pinzan, Camila Figueiredo; Marq, Jean Baptiste; Friedrich, Nikolas; Sawmynaden, Kovilen; Liew, Lloyd; Chai, Wengang; Childs, Robert A.; Saouros, Savvas; Simpson, Peter; Roque-Barreira, Maria Cristina; Feizi, Ten; Soldati‐Favre, Dominique; Matthews, Stephen

doi:10.1074/jbc.m111.325928

Cited by 41 publications

(46 citation statements)

References 60 publications

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“…The probes were robotically printed in duplicate on nitrocellulose-coated glass slides at 2 and 5 fmol per spot using a non-contact instrument [38], [39]. The his-tagged recombinant VP1 protein was pre-complexed with mouse monoclonal anti-poly-histidine (Ab1) and biotinylated anti-mouse IgG antibodies (Ab2) (both from Sigma) in a ratio of 4∶2∶1 (by weight).…”

Section: Methodsmentioning

confidence: 99%

Structures of B-Lymphotropic Polyomavirus VP1 in Complex with Oligosaccharide Ligands

et al. 2013

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B-Lymphotropic Polyomavirus (LPyV) serves as a paradigm of virus receptor binding and tropism, and is the closest relative of the recently discovered Human Polyomavirus 9 (HPyV9). LPyV infection depends on sialic acid on host cells, but the molecular interactions underlying LPyV-receptor binding were unknown. We find by glycan array screening that LPyV specifically recognizes a linear carbohydrate motif that contains α2,3-linked sialic acid. High-resolution crystal structures of the LPyV capsid protein VP1 alone and in complex with the trisaccharide ligands 3′-sialyllactose and 3′-sialyl-N-acetyl-lactosamine (3SL and 3SLN, respectively) show essentially identical interactions. Most contacts are contributed by the sialic acid moiety, which is almost entirely buried in a narrow, preformed cleft at the outer surface of the capsid. The recessed nature of the binding site on VP1 and the nature of the observed glycan interactions differ from those of related polyomaviruses and most other sialic acid-binding viruses, which bind sialic acid in shallow, more exposed grooves. Despite their different modes for recognition, the sialic acid binding sites of LPyV and SV40 are half-conserved, hinting at an evolutionary strategy for diversification of binding sites. Our analysis provides a structural basis for the observed specificity of LPyV for linear glycan motifs terminating in α2,3-linked sialic acid, and links the different tropisms of known LPyV strains to the receptor binding site. It also serves as a useful template for understanding the ligand-binding properties and serological crossreactivity of HPyV9.

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Section: Methodsmentioning

confidence: 99%

Structures of B-Lymphotropic Polyomavirus VP1 in Complex with Oligosaccharide Ligands

et al. 2013

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“…Genetic disruption of each one of these three genes does not interfere with parasite survival [8] nor its interaction with, and attachment to, host cells [10]; however, MIC1 has been shown to play a role in invasion and contributes to virulence in mice [10]. We previously isolated soluble MIC1/4, a lactose-binding complex from soluble T. gondii antigens (STAg) [17], and its lectin activity was confirmed by the ability of MIC1 to bind sialic acid [9] and MIC4 to β-galactose [18]. We also reported that MIC1/4 stimulates adherent splenic murine cells to produce IL-12 at levels as high as those induced by STAg [20].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown that host-cell invasion by apicomplexan parasites such as T. gondii involves carbohydrate recognition [12–15]. Interestingly, MIC1 and MIC4 have lectin domains [11, 16–18] that recognize oligosaccharides with sialic acid and D-galactose in the terminal position, respectively. Importantly, the parasite’s Lac + subcomplex, consisting of MIC1 and MIC4, induces adherent spleen cells to release IL-12 [17], a cytokine critical for the protective response of the host to T. gondii infection [19].…”

Section: Introductionmentioning

confidence: 99%

The lectin-specific activity ofToxoplasma gondiimicroneme proteins 1 and 4 binds Toll-like receptor 2 and 4 N-glycans to regulate innate immune priming

Sardinha-Silva

Mendonça-Natividade

Pinzan

et al. 2017

Preprint

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“…3; 150 < ' < 170 and À10 < < 10 ). The TgMIC4 structure was determined by solution NMR, and LNB was modelled by calculation using a molecular docking program (HADDOCK) based on NOEderived distance restraints (Marchant et al, 2012). The type-1 A tetrasaccharide in GH98 EABase mutants contains an LNB in which the sugars adopt an L-shaped conformation (Fig.…”

Section: Glycosidic Bond Conformationsmentioning

confidence: 99%

Conformations of the type-1 lacto-N-biose I unit in protein complex structures

Fushinobu

2018

Acta Cryst Sect F

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The lacto-N-biose I (Galβ1-3GlcNAc; LNB) disaccharide is present as a core unit of type-1 blood group antigens of animal glycoconjugates and milk oligosaccharides. Type-1 antigens often serve as cell-surface receptors for infection by pathogens. LNB in human milk oligosaccharides functions as a prebiotic for bifidobacteria and plays a key role in the symbiotic relationship of commensal gut microbes in infants. Protein Data Bank (PDB) entries exhibiting the LNB unit were investigated using the GlycoMapsDB web tool. There are currently 159 β-LNB and nine α-LNB moieties represented in ligands in the database. β-LNB and α-LNB moieties occur in 74 and six PDB entries, respectively, as NCS copies. The protein and enzyme structures are from various organisms including humans (galectins), viruses (haemagglutinin and capsid proteins), a pathogenic fungus, a parasitic nematode and protist, pathogenic bacteria (adhesins) and a symbiotic bacterium (a solute-binding protein of an ABC transporter). The conformations of LNB-containing glycans in enzymes vary significantly according to their mechanism of substrate recognition and catalysis. Analysis of glycosidic bond conformations indicated that the binding modes are significantly different in proteins adapted for modified or unmodified glycans.

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Galactose Recognition by the Apicomplexan Parasite Toxoplasma gondii

Cited by 41 publications

References 60 publications

Structures of B-Lymphotropic Polyomavirus VP1 in Complex with Oligosaccharide Ligands

Structures of B-Lymphotropic Polyomavirus VP1 in Complex with Oligosaccharide Ligands

The lectin-specific activity ofToxoplasma gondiimicroneme proteins 1 and 4 binds Toll-like receptor 2 and 4 N-glycans to regulate innate immune priming

Conformations of the type-1 lacto-N-biose I unit in protein complex structures

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