COILED-COIL FIBROUS DOMAINS MEDIATE LIGAND-BINDING BY MACROPHAGE SCAVENGER RECEPTOR TYPE-II

THE macrophage scavenger receptor, which has been implicated in the pathogenesis of atherosclerosis1,2, has an unusually broad binding specificity1. Ligands include modified low-density lipoprotein and some polyanions (for example, poly(I) but not poly(C)). The scavenger receptor type I (ref. 3) has three principal extracellular domains that could participate in ligand binding: two fibrous coiled-coil domains (α-helical coiled-coil domain IV and collagen-like domain V), and the 110-amino-acid cysteine-rich C-terminal domain VI. We have cloned complementary DNAs encoding a second scavenger receptor which we have termed type II. This receptor is identical to the type I receptor, except that the cysteine-rich domain is replaced by a six-residue C terminus. Despite this truncation, the type II receptor mediates endocytosis of chemically modified low-density lipoprotein with high affinity and specificity, similar to that of the type I receptor. Therefore one or both of the extracellular fibrous domains are responsible for the unusual ligand-binding specificity of the receptor. © 1990 Nature Publishing Group.