Structures and high and low affinity ligand binding properties of murine type I and type II macrophage scavenger receptors.

Abstract

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.

• Authors: J Ashkenas, M Penman, E Vasile, S Acton, M Freeman, M Krieger
• Journal: Journal of lipid research (J Lipid Res) Vol. 34 Issue 6 Pg. 983-1000 (Jun 1993) ISSN: 0022-2275 [Print] United States
• PMID: 8394868 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ligands
• MSR1 protein, human
• Msr1 protein, mouse
• Receptors, Cell Surface
• Receptors, Immunologic
• Receptors, Scavenger
• Scavenger Receptors, Class A

Topics

• Amino Acid Sequence
• Animals
• Base Sequence
• CHO Cells
• Cattle
• Cloning, Molecular
• Cricetinae
• Exons
• Genetic Code
• Humans
• Introns
• Ligands
• Mice
• Molecular Sequence Data
• Protein Structure, Tertiary
• Rabbits
• Receptors, Cell Surface (chemistry, genetics, metabolism)
• Receptors, Immunologic
• Receptors, Scavenger
• Scavenger Receptors, Class A
• Sequence Homology, Amino Acid