CRYSTALLOGRAPHY OF ACTIN AND RELATED PROTEINS

肌动蛋白及相关蛋白质的晶体学

• 批准号: 6180228
• 负责人: CLARENCE E SCHUTT
• 金额: $ 27.96万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6180228
• 关键词: Arabidopsis; X ray crystallography; actin binding protein; actins; biological signal transduction; cell motility; conformation; crystallization; gelsolin; intermolecular interaction; ligands; microfilaments; physical model; plant proteins; polymerization; protein isoforms; protein purification; protein structure function; recombinant proteins; structural biology

DESCRIPTION: The major goal of this grant is to understand the role of actin in producing cytoplasmic movement and to provide structural insights on the protein:protein interactions that link signal transduction pathways to the actin-based cytoskeleton. A 1.7 Angstrom resolution structure of the profilin:actin complex will allow the elucidation of water-mediated networks in the interdomain cleft of the actin molecule. A crystal structure of human profilin II will help explain why the brain form of this abundant actin-binding protein binds poly-L-proline more tightly than human profilin I. Structures of plant and mammalian profilins with bound proline-rich sequences will provide important structural parameters on links between signalling proteins and the actin cytoskeleton. The purification of short oligomers of filamentous actin suitable for x-ray crystallography will set the stage for a structure determination of the most physiologically relevant form of actin. Actin is found in high abundance in all eukaryotic cells. More than 100 different proteins bind actin to regulate polymerization or to control its role or position in various cytoskeletal structures. High resolution structural data on the profilin:poly-L-proline interaction will be important for drug design efforts in the cases of diseases where cell motility or cortical shape changes play a role (cancer, hypercoagulable platelets, lymphocytosis, viral infections, growth cone neuropathies) and for understanding the formation of organs and limbs. Many bacterial and viral pathogens exploit the actin-rich cytoskeleton to invade eukaryotic cells, and knowledge of these mechanisms will enable new therapeutic models to be developed. Actin is a major constituent of muscle cells of all forms (cardiac, skeletal, smooth), and it is essential to have the highest resolution structures possible in order to understand in chemical terms how muscle performs work at high efficiency through a broad range of load and speed. Neurons and glial cells have high concentrations of actin at their dynamic peripheries and brain profilin II serves as a link between surface activity and the cytoskeleton. Knowledge of these structures will profoundly impact neurobiology. Profilin from plant pollen is a potent allergen. Structures of plant profilin complexed with endogenous flavonols could lead to improved molecular level understanding of the IgE response in allergic individuals.

描述：该补助金的主要目标是了解 肌动蛋白在产生细胞质运动和提供结构的见解 蛋白质上：连接信号转导通路的蛋白质相互作用 与肌动蛋白细胞骨架的联系 一个1.7埃分辨率的结构， profilin：actin复合物将允许阐明水介导的网络 在肌动蛋白分子的域间裂缝中。 的晶体结构 人类profilin II将有助于解释为什么这种丰富的大脑形式， 肌动蛋白结合蛋白与聚-L-脯氨酸的结合比人profilin更紧密 I.富含结合脯氨酸的植物和哺乳动物profilins的结构 序列将提供重要的结构参数之间的联系 信号蛋白和肌动蛋白细胞骨架。 短的净化 适合于X射线晶体学的丝状肌动蛋白寡聚体将 用于最生理相关的结构测定的阶段 肌动蛋白的形式。 肌动蛋白在所有真核细胞中都有很高的丰度。 超过100种不同的蛋白质结合肌动蛋白来调节聚合或 控制其在各种细胞骨架结构中的作用或位置。 高 关于profilin：poly-L-proline相互作用的分辨率结构数据将 对于那些细胞 运动性或皮质形状变化起作用（癌症，高凝性 血小板、淋巴细胞增多症、病毒感染、生长锥神经病）和 来理解器官和肢体的形成。 许多细菌和 病毒病原体利用富含肌动蛋白的细胞骨架侵入真核细胞 细胞，这些机制的知识将使新的治疗模型 有待开发。 肌动蛋白是所有形式的肌肉细胞的主要成分 （心脏，骨骼，光滑），并且必须具有最高的 解析结构的可能性，以便在化学术语中理解 肌肉通过广泛的负荷以高效率进行工作， 速度 神经元和神经胶质细胞在其生长期具有高浓度的肌动蛋白 动态周边和大脑profilin II作为一个表面之间的联系 活性和细胞骨架。 了解这些结构将 深刻影响神经生物学。 植物花粉中的Profilin是一种有效的 过敏原 植物profilin与内源性黄酮醇复合物的结构 可能会导致提高分子水平的IgE反应的理解， 过敏的人。