Mouse LSECtin as a model for a human Ebola virus receptor.
The biochemical properties of mouse LSECtin, a glycan-binding receptor that is a member of the C-type lectin family found on sinusoidal endothelial cells, have been investigated. The C-type carbohydrate-recognition domain of mouse LSECtin, expressed in bacteria, has been used in solid-phase binding assays, and a tetramerized form has been used to probe a glycan array. In spite of sequence differences near the glycan-binding sites, the mouse receptor closely mimics the properties of the human receptor, showing high affinity binding to glycans bearing terminal GlcNAcβ1-2Man motifs. Site-directed mutagenesis has been used to confirm that residues near the binding site that differ between the human and the mouse proteins do not affect this binding specificity. Mouse and human LSECtin have been shown to bind Ebola virus glycoprotein with equivalent affinities, and the GlcNAcβ1-2Man disaccharide has been demonstrated to be an effective inhibitor of this interaction. These studies provide a basis for using mouse LSECtin, and knockout mice lacking this receptor, to model the biological properties of the human receptor.
Division of Molecular Biosciences, Department of Life Sciences, Imperial College, London, UK.
Zoi
Z
Pipirou
Alex S
AS
Powlesland
Imke
I
Steffen
Stefan
S
Pöhlmann
Maureen E
ME
Taylor
Kurt
K
Drickamer
D000818:Animals; D001665:Binding Sites; D029043:Ebolavirus / Q000737:chemistry* / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
C505228:CLEC4G protein, human; D006023:Glycoproteins; C561095:LSECtin protein, mouse; D037181:Lectins, C-Type; D011991:Receptors, Virus; D014764:Viral Proteins; C110613:secreted glycoprotein, Ebola virus
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