Probing transcriptional activation at the molecular level

在分子水平上探测转录激活

• 批准号: 10594975
• 负责人: ANNA K. MAPP
• 金额: $ 43.86万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10594975
• 关键词: Address; Binding; Biology; Cells; Chemicals; Complex; Epigenetic Process; Funding; Genetic Transcription; In Vitro; Intervention; Label; Malignant Neoplasms; Metabolic Diseases; Modeling; Molecular; Molecular Conformation; Pathway interactions; Polymerase; Process; Protein Dynamics; Research; Role; Therapeutic; Transcription Coactivator; Transcription Process; Transcriptional Activation; drug discovery; human disease; molecular modeling; molecular recognition; protein protein interaction; tool

Project Summary Much of the assembly process of the transcription machinery is governed by transient and dynamic protein- protein interactions (PPIs) that defy standard characterization strategies. Transcriptional coactivators are the hubs of this process, interacting with transcriptional activators, epigenetic modulators, the polymerase, and other coactivators to assemble the transcriptional machine. Coactivators also represent a central molecular recognition conundrum, as the mechanisms by which they interact with such a diverse array with binding partners and the influence of local binding interactions on longer-range structural and functional trajectories. In the previous funding period, we developed a molecular recognition model that addresses the first part of the conundrum. Here will build on this model to discover allosteric modulators of coactivators previously labelled undruggable despite their central functional roles. Additionally, we will answer the latter half of the conundrum to develop a comprehensive model of molecular recognition in transcriptional coactivator function.

项目总结