Structures and high and low affinity ligand binding properties of murine type I and type II macrophage scavenger receptors.
Macrophage scavenger receptors have been implicated in various macrophage-associated processes, including atherosclerosis and clearance of bacterial endotoxin. They bind to a wide variety of polyanionic ligands and display complex binding characteristics. cDNAs from the murine macrophage-like cell line P388D1 encoding the full-length type I and type II murine scavenger receptors were cloned, sequenced, and expressed in Chinese hamster ovary cells. A fragment of the corresponding murine genomic DNA was also cloned, partially sequenced, and the positions of the cloned intron/exon boundaries were determined. Comparisons of the murine scavenger receptors' sequences with the bovine, rabbit, and human sequences were used to refine a multidomain model of these trimeric, fibrous, membrane receptors. Metabolic labeling/immunoprecipitation experiments showed that most of the macrophage scavenger receptor protein expressed by P388D1 cells was the N-glycosylated type II receptor; only small amounts of type I receptor were detected. Analysis of the binding properties of the receptors provided evidence that such differential expression of the type I and type II forms may have functional significance. There were substantial receptor-type (I vs. II), as well as receptor-species (bovine vs. murine), differences in the inhibition of 125I-labeled AcLDL (acetylated low density lipoprotein) binding by ReLPS, a form of bacterial endotoxin. These differences arose, in part, because these receptors exhibited both high (Kd1(4 degrees C) = 0.05-0.2 micrograms protein/ml) and low (Kd2(4 degrees C) = 2.5-12.8 micrograms protein/ml) affinity binding of 125I-labeled AcLDL. The ability of ReLPS (1 mg/ml) to inhibit either or both of these two classes of binding interactions varied depending on the species and type of receptor.
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
J
J
Ashkenas
M
M
Penman
E
E
Vasile
S
S
Acton
M
M
Freeman
M
M
Krieger
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002417:Cattle; D003001:Cloning, Molecular; D006224:Cricetinae; D005091:Exons; D005815:Genetic Code; D006801:Humans; D007438:Introns; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D017386:Sequence Homology, Amino Acid
D008024:Ligands; C495139:MSR1 protein, human; C495140:Msr1 protein, mouse; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A