Impact of heme and heme degradation products on peptides and proteins

血红素和血红素降解产物对肽和蛋白质的影响

• 批准号: 214878445
• 负责人: Professorin Dr. Diana Imhof, Ph.D.
• 金额: --
• 依托单位: Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/214878445?language=en
• 关键词: Impact; heme; degradation; products; peptides

Heme is increasingly recognized as an essential effector molecule in biological processes where it is bound either permanently or temporarily to a wide range of proteins. These interactions are mediated by heme-binding motifs and heme-regulatory motifs. In an effort to functionally and structurally characterize these motifs with respect to their heme binding capacity and binding modes we are applying a panel of spectroscopic methods (UV/Vis, Raman, EPR, CD, NMR) using combinatorial library- and literature-derived peptides in the first approach, which subsequently is to be extended to suitable heme-protein complexes. This includes the establishment of applicable protein-based test systems allowing for investigating if protein function is altered by the heme molecule. These results will allow for a transfer of knowledge obtained on the peptide level to the protein level. On the other hand, degradation of heme is known to cause the formation of so-called heme degradation products (HDPs). These compounds will be examined for their potential to structurally and functionally influence peptides and proteins upon binding to the respective sequence stretches. This study will shed light on the essential determinants occurring in proteins that are responsible for HDP interaction and resulting conformational and functional changes. Subsequently, the information acquired from both individual approaches supplements the prerequisites for developing suitable heme and HDP detection systems. Such systems will facilitate the implementation of a diagnostic tool to monitor heme and HDP concentration in pathophysiological conditions such as cerebral vasospasm and other disorders related to an unphysiological increase of these molecules.

血红素越来越被认为是生物过程中的一种重要效应分子，它永久或暂时地与多种蛋白质结合。这些相互作用由血红素结合基序和血红素调节基序介导。为了在功能和结构上表征这些基序的血红素结合能力和结合模式，我们正在应用一组光谱方法（UV/维斯，拉曼，EPR，CD，NMR）使用组合库和文献衍生的肽在第一种方法，随后被扩展到合适的血红素-蛋白质复合物。这包括建立适用的基于蛋白质的测试系统，以研究血红素分子是否改变了蛋白质功能。这些结果将允许在肽水平上获得的知识转移到蛋白质水平。另一方面，已知血红素的降解导致形成所谓的血红素降解产物（HDPs）。将检查这些化合物在与相应序列段结合后在结构和功能上影响肽和蛋白质的潜力。这项研究将阐明蛋白质中发生的重要决定因素，负责HDP相互作用和由此产生的构象和功能变化。随后，从这两个单独的方法获得的信息补充了开发合适的血红素和HDP检测系统的先决条件。这样的系统将促进诊断工具的实施，以监测在病理生理条件下的血红素和HDP浓度，例如脑血管痉挛和与这些分子的非生理性增加相关的其他病症。