CHEM SYNTH & HIGH RES CRYSTAL STRUCT OF POTENT ANTI HIV PROTEIN AOP RANTES

化学合成

• 批准号: 6205778
• 负责人: ALEX WLODAWER
• 金额: --
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6205778
• 关键词: biological products; biomedical resource; musculoskeletal system; proteins; spectrometry

Actin crosslinking proteins organize filamentous (F-) actin into higher order assemblies such as bundles and networks which are important for biological processes including cell motility, cytokinesis and tumorigenesis. Fimbrin is a representative member of the largest superfamily of actin crosslinkers which is characterized by a conserved 275 amino acid F-actin binding domain. We have determined the crystal structure of the N-terminal actin binding domain of human fimbrin (ABD1) to 2.4 E resolution, which represents the first high resolution structure of an actin-crosslinking domain. Initial characterization of ABD1 crystals was performed using synchrotron radiation at Brookhaven National Laboratory, Beamline X9B, where the crystals diffracted to at least 1.9 E resolution. ABD1 is an ellipsoid molecule of dimensions (60x40x40E 3, and has a novel fold Hcomposed of two calponin homology (CH) subdomains. CH domains may Hserve to target a number of proteins, including signaling proteins, to Hcytoskeletal components. In collaboration with David DeRosier, we Hhave now docked this x-ray structure into the 28E electron microscopic Hreconstruction of actin filaments decorated with a comparable Hfragmenet of fimbrin. This work has for the first time provided an Hatomic model for the crosslinked assembly.

肌动蛋白交联蛋白将丝状（F-）肌动蛋白组织成 更高阶的集合，例如束和网络， 对于包括细胞运动在内的生物过程很重要， 胞质分裂和肿瘤发生。 Fimperial是一个代表性的成员， 最大的肌动蛋白交联剂超家族，其特征在于 由保守的275个氨基酸的F-肌动蛋白结合域。 我们有 确定了N-末端肌动蛋白结合的晶体结构 2.4 E分辨率，其代表 肌动蛋白交联域的第一高分辨率结构。 ABD 1晶体的初始表征使用 布鲁克海文国家实验室的同步辐射，光束线X9 B， 其中晶体衍射到至少1.9E分辨率。 ABD 1是 尺寸为60 x40 x40 E 3的椭圆体分子，具有新颖的折叠 H由两个Calponin同源（CH）亚结构域组成。 CH结构域可以 Hserve针对许多蛋白质，包括信号蛋白， 到细胞骨架成分。 我们与大卫·德罗西尔合作 Have现在docked对接this x-ray射线structure结构into the 28 E electron电子 显微镜下用一种修饰的肌动蛋白丝的H 类似的Hfragmenet。 这项工作首次 提供了交联组装的Hatomic模型。