A cysteine-rich domain of the “mannose” receptor mediates GalNAc-4-SO4 binding

A cysteine-rich domain of the “mannose” receptor mediates GalNAc-4-SO₄ binding

Department of Pathology, Washington University Medical School, St. Louis, MO 63110

Edited by Phillips W. Robinson, Massachusetts Institute of Technology, Cambridge, MA, and approved December 16, 1997 (received for review November 10, 1997)

Abstract

A critical element of lutropin bioactivity in vivo is its rapid removal from the blood by a receptor, located in hepatic endothelial cells, that recognizes the terminal sulfated carbohydrate structure SO₄-4-GalNAcβ1,4GlcNAcβ1,2Manα (S4GGnM). We have previously shown that the macrophage mannose (Man)-receptor cDNA directs the synthesis of a protein that binds oligosaccharides with either terminal S4GGnM or terminal Man, at independent sites. We now show that the cysteine-rich (Cys-Rich) domain at the N terminus of the Man/S4GGnM receptor accounts for binding of oligosaccharides with terminal GalNAc-4-SO₄, whereas calcium-dependent carbohydrate recognition domains (CRDs) account for binding of ligands containing terminal Man. The Cys-Rich domain is thus a previously unrecognized carbohydrate binding motif. Cys-Rich domains have been described on the three other members of the endocytic C-type lectin family of receptors. The structural relationship of these receptors to the Man/S4GGnM receptor raises the possibility that their Cys-Rich domains also bind carbohydrate moieties and contribute to their function.

Footnotes

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Abbreviations: Man, mannose; Man-R, mannose receptor; S4GGnm, SO₄-4-GalNAcβ1,4GlcNAcβ1,2Manα; S4GGnM-R, SO₄-4-GalNAcβ1,4GlcNAcβ1,2Manα-receptor; CHO, Chinese hamster ovary; Cys-Rich, cysteine-rich; CRDs, carbohydrate recognition domains; FN-II, fibronectin type II; LH, lutropin.