A Small Region of the Natural Killer Cell Receptor, Siglec-7, Is Responsible for Its Preferred Binding to α2,8-Disialyl and Branched α2,6-Sialyl Residues

By T. Yamaji, Takane Teranishi, M. Alphey, P. Crocker, Y. Hashimoto. Journal of Biological Chemistry, 2002

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Siglec-7 is a sialic acid-binding lectin recently identified as an inhibitory receptor on natural killer cells. Here we characterize the sugar-binding specificity of Siglec-7 expressed on Chinese hamster ovary cells using polyvalent streptavidin-based glyco-probes. Glyco-probes carrying unique oligosaccharide structures such as GD3 (NeuAcα2,8NeuAcα2,3Galβ1,4Glc) and LSTb (Galβ1,3[NeuAcα2,6]GlcNAcβ1,3Galβ1,4Glc) oligosaccharides bound to Siglec-7 better than those carrying LSTc (NeuAcα2,6Galβ1,4GlcNAcβ1,3Galβ1,4Glc) or GD1a (NeuAcα2,3Galβ1,3GalNAcβ1,4[NeuAcα2,3]Galβ1,4Glc) oligosaccharides. In contrast, Siglec-9, which is 84% identical to Siglec-7, did not bind to the GD3 and LSTb probes but did bind to the LSTc and GD1a probes. To identify a region(s) responsible for their difference in binding specificity, we prepared a series of V-set domain chimeras between Siglecs-7 and -9. Substitution of a small region, Asn70–Lys75, of Siglec-7 with the equivalent region of Siglec-9 resulted in loss of Siglec-7-like binding specificity and acquisition of Siglec-9-like binding properties. In comparison, a Siglec-9-based chimera, which contains Asn70–Lys75 with additional amino acids derived from Siglec-7, exhibited Siglec-7-like specificity. These results, combined with molecular modeling, suggest that the C-C′ loop in the sugar-binding domain plays a major role in determining the binding specificities of Siglecs-7 and -9.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/faec1fd19628ec26ef881a66b21db573e2b65ff6

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