Biophysics of Protein Disorder and Complexity, Single Molecules to Mesoscales

蛋白质无序和复杂性的生物物理学，从单分子到中尺度

• 批准号: 10320842
• 负责人: Ashok A Deniz
• 金额: $ 48.38万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320842
• 关键词: Address; Aging; Area; Binding; Biochemistry; Biology; Biophysical Process; Biophysics; Cell physiology; Cells; Cellular biology; Complex; Disease; Future; Goals; In Vitro; Lead; Light; Link; Malignant Neoplasms; Membrane; Organelles; Parkinson Disease; Peptides; Phase; Proteins; Proteome; System; Work; alpha synuclein; biological systems; experimental study; improved; single molecule; tool

Intrinsically disordered proteins (IDPs) comprise a significant fraction of eukaryotic proteomes, and are critical for cellular function and several diseases. They are also involved in the formation and dynamics of membraneless organelles (MLOs) that are important for cellular biochemistry. Several important open questions remain to be answered regarding the detailed biophysics of IDPs and MLOs. Addressing these questions is the overall goal of the proposed work. Building on our past and ongoing efforts in this area, we will carry out work in several directions. Using peptide and protein systems that are linked to ALS and cancer, we will use both single-molecule and ensemble experiments to probe important aspects of these systems, including understanding the interplay of intra- and inter-molecular interactions, effects of reentrant transitions and asymmetries in the phase diagrams, and aging in droplet systems. We will also carry out experiments on understanding membrane-induced binding-folding and aggregation of the Parkinson’s disease related protein α-synuclein. Single-molecule tools will also be improved or further developed as needed during the project. These directions will also lead to more complex experiments both in vitro and in cells at later stages of the work or in future experiments. Overall, the proposed work is anticipated to lead to an improved understanding of the biophysical mechanisms underlying the cell biology and disease relevance of these important biological systems.

胞内无序蛋白（IDP）是真核生物蛋白质组的重要组成部分， 并且对细胞功能和几种疾病至关重要。他们还参与了 无膜细胞器（MLO）的形成和动力学，对细胞的生长至关重要。 生物化学关于详细的信息，仍有几个重要的未决问题有待回答。 国内流离失所者和MLO的生物物理学。解决这些问题是拟议的 工作在我们过去和目前在这一领域所作努力的基础上，我们将在几个领域开展工作， 方向使用与ALS和癌症相关的肽和蛋白质系统，我们将使用 单分子和系综实验来探测这些系统的重要方面， 包括理解分子内和分子间相互作用的相互作用， 相图中的重入转变和不对称性，以及液滴系统中的老化。我们 还将进行理解膜诱导的结合折叠的实验， 帕金森病相关蛋白α-突触核蛋白的聚集。单分子工具将 在项目过程中，也可以根据需要进行改进或进一步开发。这些方向也将 导致更复杂的实验，无论是在体外和细胞中的后期阶段的工作， 未来的实验总的来说，拟议的工作预计将改善 了解细胞生物学和疾病相关性的生物物理机制 这些重要的生物系统。