布斯特拉米德A-actin复合物的结构,分辨率为1.35安格斯特罗姆
Syed Alipayam Rizvi1, Valentina Tereshko, Anthony A Kossiakoff
1Department of Chemistry, University of Chicago, Chicago, Illinois 60637, USA.
Journal of the American Chemical Society
|March 23, 2006
概括
比斯特拉米德A与乙烯酸结合,揭示了它的抗增殖机制. 这种结构洞察力有助于开发新的actin细胞骨架探针和治疗线索.
科学领域:
- 海洋天然产品化学 海洋天然产品化学
- 结构生物学是结构生物学.
- 生物化学 生物化学
背景情况:
- 比斯特拉米德A是一种来自Lissoclinum bistratum的强效抗增殖海洋天然产品,其主要细胞受体是actin.
- 了解Bistramide A与actin的相互作用对于其治疗潜力至关重要.
研究的目的:
- 为了确定比斯特拉米德A与单质actin结合的X射线结构.
- 为了阐明比斯特拉米德A的抗增殖活性的分子机制.
- 为开发新型比斯特拉米德A类似物提供基础.
主要方法:
- 在1.35A分辨率的Bistramid A-actin复合物的X射线晶体学.
- 结合界面和结合网络的结构分析.
- 比斯特拉米德框架的化学修改.
主要成果:
- X射线结构显示,Bistramide A深入穿透了1和3子域之间的actin结合裂.
- 在结合时形成了一个广泛的结网.
- 这种结构为Bistramide A对G-actin聚合物的调节提供了第一个洞察力.
结论:
- 确定的结构阐明了Bistramide A在原子分辨率上与actin的相互作用.
- 这些结构信息是了解比斯特拉米德A的作用机制的关键.
- 这些发现支持合成类型的合理设计,用于研究actin细胞骨和作为潜在的治疗方法.
相关概念视频
Newman Projections
Different notations are used to represent the three-dimensional structure of molecules on two-dimensional surfaces. One of the most commonly used representations is the dash-wedge formula. The dashed wedges, solid wedges, and the plane lines indicate the groups situated behind the plane, coming out of the plane, and in the plane, respectively.
The organic molecules rotate across the single bonds leading to numerous temporary three-dimensional structures of varying energy known as conformers.
The organic molecules rotate across the single bonds leading to numerous temporary three-dimensional structures of varying energy known as conformers.
Introduction to Actin
Actin is a highly conserved cytoskeletal protein found abundantly in eukaryotic cells. It constitutes 10% weight of the total cellular protein in muscle cells, while in non-muscle cells, it is lower and makes up around 1–5 percent of the total cell protein. Actin found in the unicellular amoebae and complex multicellular animals is around 80% similar, demonstrating their conservation over a billion years of evolution. Actin coding genes are conserved within species and across different species.
Actin Polymerization
Actin polymerization occurs through the head-to-tail association of binding sites on monomeric actin or G-actin to form filamentous or F-actin. The polymerization can be divided into three phases ̶ nucleation, elongation, and steady-state phase.
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight actin...
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight actin...
Generation of Straight or Branched Actin Filaments
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Formation of Higher-order Actin Filaments
The polymerization of G-actin monomers into filamentous F-actin is a multi-step process. Once the F-actins are formed, they can bundle together in different arrangements to form higher-order networks and regulate cellular functions. Common examples include the formation of lamellipodia and filopodia at the cell's leading edge by actin reorganization in a migrating cell. The microvilli on the brush border epithelial cells are also formed through the F-actin network.
The high-order actin networks...
The high-order actin networks...
The Structure of Intermediate Filaments
The intermediate filaments are one of three widely studied cytoskeletal filaments. They are so named as their diameter (10 nm) is in between that of microfilaments (7 nm) and the microtubules (25 nm). These filaments are highly stable and can remain intact when exposed to high salt concentrations and detergents. These filaments are responsible for providing stability and mechanical support to the cells. They also help in cell adhesion and maintaining tissue integrity.
Intermediate filaments...
Intermediate filaments...


