Pattern recognition receptors (PRRs) encompass several classes of cell surface, cytoplasmic 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 in addition to pathogens. Our group has begun structural investigations of cell surface 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 as well as proteins purified from animal tissues. 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.