CRYSTALLOGRAPHY OF ACTIN AND RELATED PROTEINS

建议确定优于1.7埃的分辨率， 使用X射线的profilin：beta-actin复合物的晶体结构 晶体学，使用时间分辨劳厄衍射来表征 在profilin：β-肌动蛋白晶体中可诱导的广泛的结构转变， 以获得β-肌动蛋白的丝状形式的模型，并确定 profilin的结构：γ肌动蛋白，维生素D结合蛋白，和 桦树花粉蛋白。 肌动蛋白的最高可能分辨率结构对于 理解肌动蛋白在化学机械转导中的作用， 特别是肌肉收缩的过程。在非肌肉细胞中， 细胞质分裂、膜皱褶、应力纤维等基本过程 形成、微绒毛囊泡形成、变形虫运动和神经生长 视锥运动依赖于对肌动蛋白丝形成的控制， 组织成更高层次的结构。 Profilin不仅在肌动蛋白的调节中起着核心作用， 聚合，但也有酶，产生第二信使， 在细胞表面的配体-受体相互作用的反应。因此它 作为信号转导复合物之间的关键环节， 对细胞活化和肌动蛋白微丝系统的反应。的 与肌动蛋白复合profilin的结构将是重要的解开 当细胞被逆转录病毒转化时发生的细胞质事件 或生长因子，在细胞质组织中发生了巨大的变化， 和动态。 profilin：actin的结构对于理解 癌症，因为它的作用，控制外观的转化 表型。它与免疫系统在许多不同领域的作用有关。 方法，包括淋巴细胞和巨噬细胞的修补和覆盖 能动性花粉profilin的结构将有助于更深层次的 了解过敏反应。

It is proposed to determine to better than 1.7 Angstroms resolution the crystal structure of the profilin:beta-actin complex using X-ray crystallography, to use time-resolved Laue diffraction to characterize the extensive structural transitions inducible in profilin:beta-actin crystals, to obtain a model of the filamentous form of beta-actin, and to determine the structures of profilin:gamma.actin, vitamin D binding protein, and Birch pollen profilin. The highest possible resolution structure of actin is essential for understanding the role of actin in chemo-mechanical transduction and, in particular, the process of muscle contraction. In nonmuscle cells, very basic processes such as cytokinesis, membrane ruffling, stress fiber formation, microvillar vesiculation, amoeboid movements, and nerve growth cone motility depend upon control over actin filament formation and organization into higher order structures. Profilin plays a central role in the regulation not only of actin polymerization, but also of enzymes that generate second messengers in response to ligand-receptor interactions at the cell surface. It thus serves as a key link between signal transduction complexes formed in response to cellular activation and the actin microfilament system. The structure of profilin in complex with actin will be important in unraveling the cytoplasmic events occurring when a cell, transformed by retroviruses or growth factors, undergoes dramatic changes in cytoplasmic organization and dynamics. The structure of profilin:actin will be of importance in understanding cancer because of its role in controlling the appearance of the transformed phenotype. It is related to actions of the immune system in many different ways, including patching and capping of lymphocytes and macrophage motility. The structure of pollen profilin will contribute to a deeper understanding of the allergic reaction.