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）包括血清中的几类细胞表面，细胞质和可溶性受体，它们识别与病原体相关的分子模式（PAMP）。识别的弹药包括脂多糖，脂肪酸，肽聚糖，DNA，RNA，富含甘露糖的糖蛋白，真菌葡萄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，通常在抗原呈递细胞（APC）（例如巨噬细胞和树突状细胞以及血管内皮）上表达。此外，PRR通常认识到各种形式的“改变自我”，例如改良的脂蛋白，高级糖基化终产物（年龄）和凋亡细胞以及诸如二氧化硅和石棉粉尘等异物。因此，除病原体外，PRR对于检测和清除多种潜在有害的配体也很重要。我们的小组已经开始对细胞表面清道夫受体（识别改良脂蛋白的PRR的子集）以及年龄的受体进行结构研究。我们正在使用E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。我们的目标是使用X射线晶体学和各种生物物理结合研究研究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做出反应至关重要。