Regulation of NF-kB signaling through competitive interactions against linear polyubiquitin

通过与线性多聚泛素的竞争性相互作用调节 NF-kB 信号传导

• 批准号: 22K06161
• 负责人: Walinda Erik
• 金额: $ 2.66万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22K06161/
• 关键词: ubiquitin; ubiquitin binding; M1-linked chains; HOIL-1L; NZF domain; zinc finger; Ubiquitin; NF-kB signaling; Binding proteins; Chemical physics; Competitive binding

The study has progressed smoothly and produced a range of outcomes that have been disseminated through publication. Notably, the research on ubiquitin chains using molecular dynamics simulations and NMR experiments has yielded intriguing findings that support observations made by researchers in other fields, such as X-ray crystallography. Specifically, researchers have reported diverse conformations of the same ubiquitin chain under different crystallization conditions, but all of these conformations have been found to be situated along the same phase-space trajectory as identified by molecular dynamics. As a result, we are making progress in understanding the relationship between the internal dynamics of ubiquitin chains and their subsequent binding and release from ubiquitin-binding receptors. However, we are still investigating the precise kinetics of the HOIL-1L NZF-linear ubiquitin interaction and starting to comprehend how competitive processes may contribute to polyubiquitin binding selectivity and avidity. The primary outcome of the first year has been submitted for publication. However, future aspects of the study, particularly those involving chain binders other than the HOIL-1L NZF domain, are still unpublished and will be analyzed starting this year.

这项研究取得了平稳的进展，并产生了一系列通过出版物传播的结果。值得注意的是，使用分子动力学模拟和NMR实验对泛素链的研究产生了有趣的发现，这些发现支持了其他领域的研究人员（例如X射线晶体学）进行的观察结果。具体而言，研究人员在不同的结晶条件下报告了同一泛素链的各种构象，但是所有这些构型都被发现沿着分子动力学确定的相同的相位轨迹位于相同的相位轨迹。结果，我们在理解泛素链的内部动力学及其随后从泛素结合受体中释放的内部动力学之间的关系取得了进展。但是，我们仍在研究HOIL-1L NZF线性泛素相互作用的精确动力学，并开始理解竞争过程如何有助于多泛素结合的选择性和亲和力。第一年的主要结果已提交出版。但是，这项研究的未来方面，特别是涉及HOIL-1L NZF域以外的链粘合剂的方面，仍未出版，将从今年开始分析。

项目成果

Rheo‐NMR Spectroscopy for Cryogenic‐Probe‐Equipped NMR Instruments to Monitor Protein Aggregation

用于监测蛋白质聚集的配备低温探针的 NMR 仪器的流变核磁共振波谱

• DOI: 10.1002/cpz1.617
• 发表时间: 2022
• 期刊: Current Protocols
• 作者: Morimoto Daichi;Walinda Erik;Yamamoto Akihiko;Scheler Ulrich;Sugase Kenji
• 通讯作者: Sugase Kenji

混雑環境がタンパク質の構造揺らぎと異常凝集体形成に影響を与える

拥挤环境影响蛋白质结构波动和异常聚集体形成

• 发表时间: 2023
• 期刊: 月刊「細胞」
• 作者: 森本 大智;Erik Walinda;菅瀬 謙治
• 通讯作者: 菅瀬 謙治

Counter-flow phenomena studied by nuclear magnetic resonance (NMR) velocimetry and flow simulations

通过核磁共振 (NMR) 测速和流动模拟研究逆流现象

• DOI: 10.1063/5.0097543
• 发表时间: 2022
• 期刊: Physics of Fluids
• 影响因子: 4.6
• 作者: Kohn Benjamin;Walinda Erik;Sugase Kenji;Morimoto Daichi;Scheler Ulrich
• 通讯作者: Scheler Ulrich

Erik Walinda

埃里克·瓦林达

• 发表时间: 2022
• 作者: Minamino Tohru;Kinoshita Miki;Inoue Yumi;Kitao Akio;Namba Keiichi;Solution-state polyubiquitin binding specificity exhibited by the extended NZF domain of LUBAC component HOIL-1L
• 通讯作者: Solution-state polyubiquitin binding specificity exhibited by the extended NZF domain of LUBAC component HOIL-1L