血凝的晶体结构:对actin切断,封闭和核化的影响
L D Burtnick1, E K Koepf, J Grimes
1Department of Chemistry, University of British Columbia, Vancouver, Canada.
Cell
|August 22, 1997
概括
与凝蛋白结合会引起结构变化,使其能够结合乙和调节丝. 这种机制也可能与家族性氨基粉症中粉样质斑块的形成有关.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 凝索林是一种关键的活性蛋白结合蛋白,参与调节活性蛋白的动态.
- 在没有的状态下,其结构可以防止由于紧的球状包装而导致酸结合.
- 了解凝素的结构转变对于理解丝动态和相关疾病至关重要.
研究的目的:
- 为了阐明凝素依赖激活的结构基础.
- 提出凝素在丝切断,封闭和核化中的作用模型.
- 探索凝素结构,多酸酸结合和家族性粉症之间的潜在联系.
主要方法:
- 使用X射线晶体学来确定gelsolin的结构.
- 使用结构分析来了解域互动和构造变化.
- 进行了比较分析,将结构发现与功能角色和疾病机制联系起来.
主要成果:
- 凝索林的六个域在没有Ca2+的条件下形成一个紧的结构,隐藏着活性蛋白结合点.
- 建议结合可诱导域移位,释放N-和C-终端半端以进行独立的活性蛋白结合.
- 结构上的洞察力表明了丝切断,封闭和核化的机制.
- 这种结构为了解多酸酸结合和Asp-187突变在家族性粉样化症中的作用提供了基础.
结论:
- 凝中的依赖的形状变化对其活性蛋白结合和调节功能至关重要.
- 确定的结构提供了对凝在行为动态中的多样性作用的机制性见解.
- 结构特征可能解释了gelsolin在家族性amyloidosis病原体中的参与.
相关概念视频
01:42Actin 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...
01:14Generation 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...
01:19Actin Filament Depolymerization
Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
In F-actin, the ADF/cofilin proteins...
01:11Formation 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...
01:39Mechanism of Filopodia Formation
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
01:31Mechanism of Lamellipodia Formation
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...