核糖酶A的粉样纤维素,具有三维域交换和本地样结构的三维结构
Shilpa Sambashivan1, Yanshun Liu, Michael R Sawaya
1Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, Box 951570, UCLA, Los Angeles, California 90095-1570, USA.
Nature
|September 9, 2005
概括
研究人员从RNase A设计了类似粉样蛋白质的纤维,揭示了这些蛋白质聚合物可以保留与原生蛋白质类似的结构和酶活性. 这支持了纤维细胞形成的拉链-脊柱模型.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 神经退行性疾病 神经退行性疾病
背景情况:
- 粉样纤维是与神经退行性疾病相关的不溶性蛋白质聚合物.
- 纤维状"交叉β"状态的结构基础在蛋白质科学中仍然是一个基本的难题.
- 关键问题涉及不同的原生和纤维状体状态的存在以及纤维状体形成期间重新折叠的程度.
研究的目的:
- 为了研究设计的粉样纤维的结构和功能性质.
- 为了确定本地蛋白质结构和活性是否保留在纤维状聚合物中.
- 为了测试拉链-脊柱模型对粉样蛋白纤维素形成的有效性.
主要方法:
- 从酶RNase A.中设计和制造粉样纤维.
- 评估纤维结构内的分子的酶活性.
- 结构分析以确定纤维体内RNase A的构造.
主要成果:
- 成功创建了RNase A的设计型粉样纤维.
- 纤维细胞内的分子保留了与原生细胞相似的结构和酶活性.
- 功能单元包括一个核心RNase A域和一个交换补充域.
结论:
- 粉样纤维可以结合功能性,本地类型的蛋白质分子.
- 这些发现支持了拉链脊柱模型,其中交叉β脊柱是由功能性,域互换单位装饰的.
- 这挑战了纤维细胞形成总是完全失去本地蛋白质结构的观念.
相关概念视频
Protein Folding
Overview
Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
A protein's shape is critical to its function. For example, an enzyme can...
Globular and Fibrous Proteins
Many proteins can be classified into two distinct subtypes - globular or fibrous. These two types differ in their shapes and solubilities.
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Structural Protein Function
Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to form...
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to form...
Type IV Collagen of Basal Lamina
Type IV collagen is a 400 nm long, network-forming collagen that acts as a barrier between the epithelial and endothelial cells. Type IV collagen forms the backbone of the basement membrane by scaffolding with laminin, entactin, proteoglycans, and fibronectin. Apart from rendering structural support to the basement membrane, it also helps entail signaling potentials necessary for both pathological and physiological functions.
A type IV collagen molecule has six alpha chains which can exist in...
A type IV collagen molecule has six alpha chains which can exist in...
Fibrous Proteins
Fibrous proteins are either long and narrow proteins or assemble to form long and thin structures. They contain repetitive units and usually consist of either alpha helices or beta sheets and, in rare cases, a mix of both. The amino acids in the primary structure often consist of repeating amino acid sequences. The role of fibrous proteins is primarily structural. Many are located in the extracellular matrix and are present in connective tissues to impart strength and joint mobility. They are...


