滴滴生长,奥斯瓦尔德法则,和秩序的出现 在 Sarcoma 融合在 Sarcoma 中
Farkhad Maksudov1, Mauro L Mugnai2, Laura Dominguez1,3
1Department of Chemistry, The University of Texas at Austin, Austin, TX 78712.
概括
化在肉瘤中低复杂性域 (FUS-LC) 从液态过渡到凝状态,形成纤维. 这个过程,由奥斯瓦尔德指导.
科学领域:
- 生物化学 生物化学
- 生物物理学的生物物理.
- 计算生物学 计算生物学
背景情况:
- 化在肉瘤 (FUS-LC) 的低复杂性域本质上是无序的,容易发生相位分离.
- FUS-LC的相位分离导致液体状液滴的形成,这些液滴成熟为凝状状态.
- 这种成熟过程涉及有序,非多态纤维的形成.
研究的目的:
- 研究FUS-LC相分离和纤维细胞形成背后的分子机制.
- 阐明特定序列区域 (核心-1,核心-2,核心-3) 在FUS-LC组件中的作用.
- 了解控制FUS-LC冷凝液成熟的动力学和热力学.
主要方法:
- 使用粗粒度模拟来建模相位分离和纤维形成过程.
- AlphaFold被用来预测C端核-3区域的纤维结构.
- 进行了多链模拟,以分析相位行为在相同化学潜力的条件下.
主要成果:
- 粗粒模拟表明,动力学上不那么稳定的纤维状区域较早形成,与奥斯瓦尔德规则一致.
- 阿尔法折叠预测揭示了核心-3中的β-链,在滴滴形成过程中启动FUS-LC组装.
- 多链模拟表明,密度相通过核和粗形成,类似于奥斯瓦尔德成熟.
结论:
- 这项研究揭示了由特定序列元素和奥斯瓦尔德规则驱动的FUS-LC的阶段式组装机制.
- 这些发现提供了从内在无序的蛋白质中形成粉样结构的见解.
- 开发的计算方法适用于研究其他内在无序蛋白质,如TDP-43.
相关概念视频
Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Metastasis
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Rous Sarcoma Virus (RSV) and Cancer
Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Ostwald’s Dilution Law
Consider a binary electrolyte AB with a concentration ‘c’ that reversibly dissociates into its constituent ions. The degree of this dissociation is represented by ⍺. This means that the equilibrium concentration of each ionic species can be expressed as ⍺c. As well as this, the fraction of the electrolyte that remains undissociated at equilibrium is given by (1−⍺). The corresponding equilibrium concentration for this undissociated portion is then calculated as (1−⍺)c. For such solutions,...


