Scavenger Receptor C-type Lectin Binds to the Leukocyte Cell Surface Glycan Lewisx by a Novel Mechanism

Hadar Feinberg,Maureen E Taylor,William I Weis

doi:10.1074/jbc.m701624200

Hadar Feinberg, Maureen E Taylor + Show 1 more

Open Access

https://doi.org/10.1074/jbc.m701624200

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Abstract

The scavenger receptor C-type lectin (SRCL) is unique in the family of class A scavenger receptors, because in addition to binding sites for oxidized lipoproteins it also contains a C-type carbohydrate-recognition domain (CRD) that interacts with specific glycans. Both human and mouse SRCL are highly specific for the Lewis(x) trisaccharide, which is commonly found on the surfaces of leukocytes and some tumor cells. Structural analysis of the CRD of mouse SRCL in complex with Lewis(x) and mutagenesis show the basis for this specificity. The interaction between mouse SRCL and Lewis(x) is analogous to the way that selectins and DC-SIGN bind to related fucosylated glycans, but the mechanism of the interaction is novel, because it is based on a primary galactose-binding site similar to the binding site in the asialoglycoprotein receptor. Crystals of the human receptor lacking bound calcium ions reveal an alternative conformation in which a glycan ligand would be released during receptor-mediated endocytosis.

Highlights

Parallels can be drawn between scavenger receptor C-type lectin (SRCL) and the E- and P-selectin cell adhesion molecules, which mediate interactions between endothelial cells and leukocytes by binding to specific glycoprotein ligands on the leukocyte surface
There are similarities between SRCL and DC-SIGN, which is expressed on dendritic cells rather than endothelial cells, and mediates cell-cell interactions by binding to Lewisx and related oligosaccharides on leukocytes
The restricted specificity of SRCL for a narrow class of oligosaccharide ligands is unusual for receptors that utilize C-type carbohydrate-recognition domain (CRD)

Summary

EXPERIMENTAL PROCEDURES

Cloning and Expression of Mouse SRCL—The cDNA coding for mouse SRCL was amplified from a mouse lung cDNA library (Clontech). The portion of the DNA coding for the CRD, from residue 603 to the C terminus, was cloned into the pINIIIompA2 expression vector for expression in Escherichia coli as

Data collection

RESULTS

Mutant CRD

DISCUSSION

Binds to the Leukocyte a Novel Mechanism