STRUCTURE/INTERACTIONS OF ACTINS & ACTIN-BINDING PROTEIN
肌动蛋白的结构/相互作用
基本信息
- 批准号:3287441
- 负责人:
- 金额:$ 9.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1985
- 资助国家:美国
- 起止时间:1985-08-30 至 1988-07-31
- 项目状态:已结题
- 来源:
- 关键词:X ray crystallography antibody specificity chemical binding chemical structure function crosslink cytoskeleton electron microscopy fibroblasts human tissue image processing immunofluorescence technique mathematical model microinjections model design /development molecular biology muscle proteins neoplastic cell physical model polymerization stoichiometry
项目摘要
Actin is found abundantly in all eukaryotic cells, where it plays a key
role in contractile processes, and in the maintenance as well as the
dynamics of cell shape and cytoplasmic consistency. In attempts to
ultimately understand the molecular basis of these actin-based processes,
we propose to use high resolution electron microscopy and three-dimensional
(3D) image analysis and processing to develop a consistent 3D molecular
model of the functionally important actin filament, and to investigate the
structural basis of actin's specific interactions with itself and with
various contractile, regulatory and cytoskeletal proteins. Using
structural, proteinchemical, immunological and microinjection methods, we
also propose to explore the role of mutant actins isolated from stably
transformed human fibroblasts in neoplasia. Specifically, we propose to
proceed as follows:
(1) To determine a consistent 3D model of the actin molecule at the 1-2 nm
resolution level from different types of negatively stained and frozen
hydrated crystalline actin arrays.
(2) To develop a consistent 3D molecular model of the actin filament from a
variety of negatively stained and frozen hydrated actin filament arrays and
to align molecular actin models within the resulting filament 3D
reconstructions.
(3) To map binding sites for contractile, regulatory and cytoplasmic
proteins on the actin molecule via 3D structural analysis of
stoichiometrically decorated crystalline actin arrays or from co-crystals
induced from specific complexes between actin and actin-interacting
proteins.
(4) To structurally and functionally analyze several types of crosslinked
actin dimers (a) to aid in developing a consistent molecular model of the
actin filament (see 2) and (b) to understand their role in regulating actin
polymerization.
(5) To investigate the in vitro polymerization properties, 3D structure,
and in situ distribution (i.e. via immunofluorescence with mutant
actin-specific antibody) and interactions (i.e. via microinjection of
mutant actin mixtures) of mutant beta-actins isolated from transformed
human fibroblasts.
肌动蛋白在所有真核细胞中大量存在,
在收缩过程中的作用,以及在维护以及
细胞形状和细胞质一致性的动力学。 应用以企图
最终了解这些肌动蛋白为基础的过程的分子基础,
我们建议使用高分辨率电子显微镜和三维
(3D)图像分析和处理以开发一致的3D分子
模型的功能重要的肌动蛋白丝,并研究
肌动蛋白与其自身和
各种收缩、调节和细胞骨架蛋白。 使用
结构、蛋白质化学、免疫学和显微注射方法,
我还建议探讨突变肌动蛋白的作用,从稳定分离,
转化的人成纤维细胞。 具体而言,我们建议
进行如下操作:
(1)为了在1-2 nm处确定肌动蛋白分子的一致3D模型,
不同类型的负染色和冷冻的分辨率水平
水合结晶肌动蛋白阵列。
(2)为了建立一个一致的肌动蛋白丝的3D分子模型,
各种负染色和冷冻水合肌动蛋白丝阵列,
在最终的细丝3D中排列分子肌动蛋白模型,
重建。
(3)绘制收缩、调节和细胞质的结合位点,
蛋白质的肌动蛋白分子通过三维结构分析,
化学计量修饰的结晶肌动蛋白阵列或来自共晶体
由肌动蛋白和肌动蛋白相互作用之间的特定复合物诱导
proteins.
(4)对几种交联聚乙烯的结构和功能进行了分析,
肌动蛋白二聚体(a),以帮助开发一个一致的分子模型,
肌动蛋白丝(见2)和(B),以了解它们在调节肌动蛋白中的作用
聚合法
(5)为了研究体外聚合性能,三维结构,
和原位分布(即通过突变体的免疫荧光
肌动蛋白特异性抗体)和相互作用(即通过显微注射
突变肌动蛋白混合物)的突变β-肌动蛋白
人成纤维细胞。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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THOMAS D. POLLARD其他文献
THOMAS D. POLLARD的其他文献
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{{ truncateString('THOMAS D. POLLARD', 18)}}的其他基金
Actin Myosin Interactions in Cell Motility
肌动蛋白肌球蛋白在细胞运动中的相互作用
- 批准号:
7999953 - 财政年份:2010
- 资助金额:
$ 9.66万 - 项目类别:
CRYSTAL STRUCTURES OF ARP2/3 COMPLEX WITH BOUND NUCLEOTIDE AND ACTIVATOR
结合核苷酸和激活剂的 ARP2/3 复合物的晶体结构
- 批准号:
7358901 - 财政年份:2006
- 资助金额:
$ 9.66万 - 项目类别:
CRYSTAL STRUCTURES OF ARP2/3 COMPLEX WITH BOUND NUCLEOTIDE AND ACTIVATOR
结合核苷酸和激活剂的 ARP2/3 复合物的晶体结构
- 批准号:
7182487 - 财政年份:2005
- 资助金额:
$ 9.66万 - 项目类别:
THE CROSSLINKING SITE OF FLUORESCENT OREGON GREEN 488
荧光俄勒冈绿 488 的交联位点
- 批准号:
6979546 - 财政年份:2004
- 资助金额:
$ 9.66万 - 项目类别:
Structure and function of Arp 2/3 complex--Subproject 1
Arp 2/3复合体的结构与功能--子项目1
- 批准号:
6769312 - 财政年份:2003
- 资助金额:
$ 9.66万 - 项目类别:
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