Mouse LSECtin as a model for a human Ebola virus receptor

Pipirou, Zoi; Powlesland, Alex S; Steffen, Imke; Pöhlmann, Stefan; Taylor, Maureen E; Drickamer, Kurt

The observed high degree of similarity between the human and mouse proteins was not necessarily predicted based on sequence comparisons. Previous modeling studies led to the hypothesis that an important contribution to high affinity binding of terminal GlcNAcβ1-2Man residues might be interaction of the N-acetyl group with the side chain of residue Trp259 (Powlesland et al. 2008) . Surprisingly, this residue was found to be substituted by arginine in the mouse protein ( Figure 4A ). The similarity of the ligand-binding activities of the human and mouse proteins does not support the hypothesis that interactions of the aromatic side chain are important. The role of this residue was tested directly by creating mutant versions of the human CRD in which Trp259 is substituted with arginine, as found in the mouse protein, or with alanine. Comparison of binding of the wild-type and mutant proteins to the exposed terminal GlcNAcβ1-2Man disaccharides of Ebola virus glycoprotein confirmed that the absence of the tryptophan side chain does not significantly affect the interaction ( Figure 4B ).