Pattern recognition receptors (PRRs) encompass several classes of cell surface receptors and soluble receptors in serum that recognize pathogen-associated molecular patterns (PAMPs). PAMPs recognized include lipopolysaccharide, lipoteichoic acid, peptidoglycan, DNA, RNA, mannose-rich glycoproteins, fungal glucans and various bacterial surface proteins. PRRs considered part of the innate immune system and are commonly expressed on antigen presenting cells (APCs) such as macrophages and dendritic cells as well as the vascular endothelium. Furthermore PRRs often recognize various forms of """"""""altered self"""""""" such as modified lipoproteins, advanced glycation end products (AGE) and apoptotic cells as well as foreign particles such as silica and asbestos dust. Thus, PRRs are important for the detection and clearance of a wide variety of potentially harmful ligands. Our group has begun structural investigations of two scavenger receptors (a subset of PRRs that recognize modified lipoproteins) as well as a receptor for AGE. We are using E coli and insect cells for expression of both receptor and ligand fragments. Our goal is to investigate the atomic structures and ligand recognition mechanisms of PRRs using x-ray crystallography and various biophysical binding studies. This information is critical to elucidating how the innate immune system interfaces with and responds to both endogenous and environmental challenges. Recent structural results from our group include the 1.4 A crystal structure of the extracellular ligand binding domain of the vascular endothelial scavenger receptor Lox-1. We are currently examining interactions of Lox-1 and other receptors with various ligands using biophysical techniques.
| Park, HaJeung; Adsit, Floyd G; Boyington, Jeffrey C (2005) The 1.4 angstrom crystal structure of the human oxidized low density lipoprotein receptor lox-1. J Biol Chem 280:13593-9 |
