Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, United States.
J Chem Theory Comput. 2022 Apr 12;18(4):2556-2568. doi: 10.1021/acs.jctc.1c00927. Epub 2022 Feb 28.
Zinc is an essential transition metal ion that plays as a structural, functional (catalytic), and a signaling molecule regulating cellular function. Unbalanced levels of zinc in cells can result in various pathological conditions. In the current work, all-atom molecular dynamics simulations were used to study the structure-function correlation between different YiiP states embedded in a lipid bilayer. This study enabled us to develop a hypothesis on the zinc efflux mechanism of YiiP. We have created six different models of YiiP representing the stages of the ion-transport process. We found that zinc ion plays a crucial role in restraining the transmembrane domains (TMDs) of the protein. In addition, H153, located in the TMD, has been proposed to guide the zinc ion toward the ZnA site of the YiiP transporter. Understanding the molecular-level Zn-transport process sheds light on the strategies affecting intracellular transition-metal ion concentrations in order to treat diseases like diabetes and cancer.
锌是一种必需的过渡金属离子，作为结构、功能（催化）和信号分子，调节细胞功能。细胞内锌水平的不平衡会导致各种病理状况。在目前的工作中，使用全原子分子动力学模拟来研究嵌入在脂质双层中的不同 YiiP 状态的结构-功能相关性。这项研究使我们能够提出关于 YiiP 锌外排机制的假设。我们创建了六个不同的 YiiP 模型，代表离子转运过程的不同阶段。我们发现锌离子在抑制蛋白质的跨膜结构域（TMD）方面起着至关重要的作用。此外，位于 TMD 中的 H153 被提议引导锌离子朝向 YiiP 转运蛋白的 ZnA 位点。了解分子水平的 Zn 转运过程为影响细胞内过渡金属离子浓度的策略提供了启示，以治疗糖尿病和癌症等疾病。
