Structural Biology of Scavenger Receptors

清道夫受体的结构生物学

• 批准号: 6828629
• 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/6828629
• 关键词: X ray crystallography; antigen presentation; atherosclerosis; biological signal transduction; cell surface receptors; crystallization; ligands; lipid transport; low density lipoprotein; oxidized lipid; phagocytes; protein structure function; receptor binding; scavenger receptor

Scavenger receptors (SRs), commonly expressed on the surfaces of phagocytes, are a structurally diverse group of receptors that share a common theme of binding to modified lipoproteins. Biologically, SRs are important for the detection and clearance of a wide array of potentially harmful ligands such as oxidatively modified proteins and lipoproteins, advanced glycation end products (AGE), oxidatively modified phospholipids, bacterial DNA, anionic polymers, apoptotic cells, bacterial cell wall components, and foreign particles such as silica dust and asbestos. Particular attention has been focused on oxidized low density lipoprotein (oxLDL), an SR ligand thought to be significant in the pathology of atherosclerosis, oxLDL-binding SRs and on SRs involved in the transport of lipids across the cell membrane. We have begun structural investigations of three key SRs important in both of these areas in addition to a protein SR ligand involved in antigen presentation. Our goal is to analyze these receptors and receptor/ligand complexes by x-ray crystallography as a means to understand the mechanisms of ligand recognition and subsequent signal transduction through the plasma membrane. This information is critical to elucidating how phagocytes interface with and respond to both endogenous and environmental challenges. Subcloning, design of multiple constructs, and receptor expression studies in E coli are currently underway.

寻宝受体（SRS）通常在吞噬细胞的表面上表达，是一组结构上多样的受体，它们具有与修饰的脂蛋白结合的共同主题。从生物学上讲，SR对于检测和清除多种可能有害的配体（例如氧化修饰的蛋白质和脂蛋白），晚期糖基化终产物（年龄），氧化磷脂，细菌DNA，厌食细胞组合细胞，细菌细胞组合粉料和硫磺的粉尘和硫磺的粉尘和硫磺的粉尘和硫磺的粉尘和硫磺的粉尘和硫磺素很重要。特别关注的是氧化的低密度脂蛋白（OXLDL），这是一种在动脉粥样硬化，OXLDL结合SR的病理学中很重要的SR配体以及与脂质跨细胞膜运输有关的SRS。除了涉及抗原呈递的蛋白质SR配体外，我们已经开始对这两个领域重要的三个关键SRS进行结构研究。我们的目标是通过X射线晶体学分析这些受体和受体/配体复合物，作为了解配体识别的机制以及随后通过质膜转导的机制。这些信息对于阐明吞噬细胞与内源性和环境挑战的接口和反应至关重要。目前正在进行亚克隆，多种构建体的设计以及E大肠杆菌中的受体表达研究。