Structural Biology of Pattern Recognition Receptors

模式识别受体的结构生物学

• 批准号: 7327209
• 负责人: Jeffrey C Boyington
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7327209
• 关键词: Structural; Biology; Pattern; Recognition; Receptors

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.

模式识别受体 (PRR) 包括几类细胞表面、细胞质和血清中的可溶性受体，可识别病原体相关分子模式 (PAMP)。公认的PAMP包括脂多糖、脂磷壁酸、肽聚糖、DNA、RNA、富含甘露糖的糖蛋白、真菌葡聚糖和各种细菌表面蛋白。 PRR 被认为是先天免疫系统的一部分，通常在巨噬细胞和树突细胞等抗原呈递细胞 (APC) 以及血管内皮细胞上表达。此外，PRR 经常识别各种形式的“改变的自我”，例如修饰脂蛋白、晚期糖基化终产物 (AGE) 和凋亡细胞以及二氧化硅和石棉粉尘等外来颗粒。因此，除了病原体之外，PRR 对于检测和清除多种潜在有害配体也很重要。我们的小组已经开始对细胞表面清道夫受体（识别修饰脂蛋白的 PRR 子集）以及 AGE 受体进行结构研究。我们使用大肠杆菌和昆虫细胞来表达受体和配体片段以及从动物组织中纯化的蛋白质。我们的目标是利用 X 射线晶体学和各种生物物理结合研究来研究 PRR 的原子结构和配体识别机制。这些信息对于阐明先天免疫系统如何与内源性和环境挑战相互作用并做出反应至关重要。