电子冷显微镜显示了髓与乙烯酸结合的强度如何释放核酸
Kenneth C Holmes1, Isabel Angert, F Jon Kull
1Department of Biophysics, Max Planck Institute for Medical Research, 69120 Heidelberg, Germany. holmes@mpimf-heidelberg.mpg.de
Nature
|September 26, 2003
概括
肌肉收缩依赖于在ATP水解过程中与actin纤维相互作用的髓交叉桥. 这项研究揭示了actin结合如何打开核酸口袋,解释了肌肉运动中的联系.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 结构生物学 结构生物学
背景情况:
- 肌肉收缩是由肌交叉桥驱动的,这些桥梁与actin纤维循环相互作用.
- 这个过程与腺三酸盐 (ATP) 水解相结合,涉及像"动力冲击"这样的形状变化.
- 连接actin结合与核酸结合亲和力的精确分子机制尚不清楚.
研究的目的:
- 阐明在肌肉收缩过程中,actin结合和核酸结合之间的联系的分子基础.
- 了解如何作用因子结合影响肌酸菌素交叉桥对三酸氨酸 (ATP) 的亲和力.
主要方法:
- 在高分辨率电子冷显微镜 (cryo-EM) 3D重建中,将actin和myosin交叉桥的原子模型配合.
- 利用结构数据分析肌肉收缩周期期间的分子相互作用.
主要成果:
- 这项研究揭示了在actin结合后的actin结合裂的关闭和核酸结合口袋的打开之间存在结构性的合.
- 这种形状变化解释了如何与actin结合削弱了肌酸核酸相互作用.
结论:
- 这项研究提供了详细的分子解释,解释了肌酸菌素交叉桥上的actin和核酸结合点之间的功能联系.
- 了解这种机制对于理解分子水平上肌肉收缩的调节至关重要.
相关概念视频
01:26Cross-bridge Cycle
As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
01:58Mechanical Protein Functions
Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force.
01:17Studying the Cytoskeleton
The cytoskeletal architecture can be studied using different microscopic and biochemical techniques. Electron microscopy was instrumental in discovering the cytoskeletal architecture around the 1960s, which allowed obtaining structural information at a high-resolution level. However, the sample preparation procedure often limits this ability in biological samples. Several protocols have been developed over the years to optimize sample preparation. In one of the protocols known as rotary...
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.
01:16Actin 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...
01:29Relaxation of Skeletal Muscles
The period of muscle contraction primarily influences the duration of stimulation at the neuromuscular junction (NMJ), the presence of free calcium ions in the sarcoplasm, and the availability of energy or ATP to support contractions.
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open.
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open.