严格的动因-热胺-肌酸胺复合物的结构
Elmar Behrmann1, Mirco Müller, Pawel A Penczek
1Department of Physical Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany.
Cell
|July 24, 2012
概括
这项研究揭示了肌肉收缩的结构基础,详细介绍了热菌素如何在活性丝上移动,以调节肌结合. 这为遗传性肌肉病提供了洞察力.
科学领域:
- 分子和细胞生物学分子和细胞生物学
- 结构生物学 结构生物学
- 生物物理学的生物物理.
背景情况:
- 肌肉和非肌肉细胞收缩性方面,托罗普米奥辛对actin-myosin相互作用的调节至关重要.
- 热氨酸运动的精确分子机制和结构动力学尚不完全理解.
研究的目的:
- 为了确定actin-tropomyosin-myosin复合物的高分辨率结构.
- 阐明基因结构重组是托罗普米奥辛调节作用的基础.
- 提出一个模型,用于托罗普米奥辛调节的髓与actin结合.
主要方法:
- 使用冷电子显微镜确定了严格的actin-tropomyosin-myosin复合物的8 Å分辨率结构.
- 伪原子建模是通过将已知的晶体结构融入冷EM密度图中来实现的.
主要成果:
- 该综合体的详细结构模型被生成,定义了actin,tropomyosin和myosin之间的广泛接口.
- 观察到肌结合诱导了显著的23 Å转移在沿着actin丝线的tropomyosin的位置.
- 影响这种接口的突变与严重的遗传性肌肉病变有关,突出显示了它的功能重要性.
结论:
- 这项研究提供了一个结构框架,以了解热菌素在调节动因-肌酸氨酸动态中的作用.
- 这些发现为遗传性肌肉病变的发病提供了分子洞察力,这些遗传性肌肉病变与这个复合体中的突变有关.
- 基于观察到的结构变化,提出了一种新型的氨酸依赖氨酸结合调节模型.
相关概念视频
01:16Actin and Myosin in Muscle Contraction
Actin and myosin are contractile proteins that form the sarcomere found in skeletal muscle tissues for regulating muscle contraction. Actin, a globular contractile protein, interacts with myosin for muscle contraction. The skeletal tissue appears striped or striated under a microscope due to the repeated arrangement of contractile proteins actin and myosin along the length of myofibrils. Dark A bands and light I bands repeat along myofibrils, and the alignment of myofibrils in the cell causes...
01:08The Sarcomere
A sarcomere is a microscopic segment repeating in a myofibril. The sarcomere fundamentally consists of two main myofilaments: thick filaments called myosin and thin filaments called actin. These filaments interact by sliding past each other in response to stimulus. In addition to myosin and actin, several other proteins, such as tropomyosin, troponin, titin, nebulin, myomesin, α-actinin, and dystrophin, play crucial roles in regulating, structuring, and functioning of the sarcomere.
Each myosin...
Each myosin...
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...
01:15Overview of Myosin Structure and Function
Myosins are a family of molecular motor proteins, first identified in the skeletal muscles, where they are responsible for muscle contraction. Along with their role in muscle contraction, these proteins also play a role in the intracellular transport of molecules and vesicles. There are twenty-four classes of myosins based on their domain sequence and organization. Of the twenty-four, six classes (Myosin I, Myosin II, Myosin V, Myosin VI, Myosin VII, and Myosin X) have been well characterized.
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...
01:26Introduction 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.