What makes the guanidinium cation so special?

是什么让胍盐阳离子如此特别？

• 批准号: 252839646
• 负责人: Dr. Johannes Hunger
• 金额: --
• 依托单位: Max-Planck-Institut für Polymerforschung
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/252839646?language=en
• 关键词: What; makes; guanidinium; cation; so

When studying the effect of ions on the stability of proteins, simple inorganic cations follow an important rule of thumb: the higher the surface charge density of the cation the stronger the ion destabilizes proteins in solution. However, the rather bulky, organic guanidinium cation (Gdm+), having a low surface charge density, is amongst the most effective protein denaturants. Thus, Gdm+ is a prominent exception in the Hofmeister series. In recent years it became apparent that this exceptional effect of Gdm+ on proteins cannot be explained from bulk properties of aqueous guanidinium electrolytes, but must be related to the specific interaction of Gdm+ with proteins.Indeed, computer simulations suggest specific interaction of Gdm+ with model proteins. However, to date the exact mechanism how Gdm+ interacts with proteins is controversially discussed. It has been suggested that Gdm+ ions bind to the peptide backbone, interact with the positively or negatively charged protein side-chains, or cover hydrophobic fragments of the proteins. Each of these interaction mechanisms is claimed to lead to the unfolding of the protein.We will study the interaction of Gdm+ with small model proteins experimentally and test the different scenarios mentioned above. We will determine the binding strength of Gdm+ to hydrophobic moieties, charged side chains, and to the amide backbone. This will reveal the predominant unfolding mechanism and what makes the guanidinium cation such an efficient protein denaturant.

当研究离子对蛋白质稳定性的影响时，简单的无机阳离子遵循一个重要的经验法则：阳离子的表面电荷密度越高，离子使蛋白质在溶液中不稳定的能力越强。然而，具有低表面电荷密度的相当庞大的有机胍阳离子（Gdm+）是最有效的蛋白质变性剂之一。因此，Gdm+是Hofmeister系列中的一个突出例外。近年来，人们发现Gdm+对蛋白质的这种特殊作用不能用胍盐电解质的整体性质来解释，而必须与Gdm+与蛋白质的特异性相互作用有关，实际上，计算机模拟表明Gdm+与模型蛋白质的特异性相互作用。然而，迄今为止，Gdm+如何与蛋白质相互作用的确切机制是有争议的讨论。已经表明Gdm+离子结合到肽骨架上，与带正电荷或负电荷的蛋白质侧链相互作用，或覆盖蛋白质的疏水片段。这些相互作用机制中的每一种都声称会导致蛋白质的解折叠。我们将通过实验研究Gdm+与小模型蛋白质的相互作用，并测试上述不同的场景。我们将确定Gdm+与疏水部分、带电侧链和酰胺骨架的结合强度。这将揭示主要的解折叠机制，以及是什么使胍阳离子成为如此有效的蛋白质变性剂。