Svensson Oskar, Gerelli Yuri, Skepö Marie
Division of Computational Chemistry, Department of Chemistry, Science for Life Laboratory, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden.
NanoLund, Lund University, Box 118, 22100 Lund, Sweden.
J Chem Inf Model. 2025 Jul 14;65(13):7089-7101. doi: 10.1021/acs.jcim.5c00854. Epub 2025 Jul 2.
Histatins are a family of multifunctional, cationic histidine-rich saliva peptides. The most prominently represented are Histatin 1, Histatin 3, and Histatin 5. Despite considerable similarities in primary structure, the three members are known to display varied antimicrobial properties and healing abilities. This study aims to provide a detailed structural comparison of Histatin 1, Histatin 3, and Histatin 5, as well as a thorough investigation into the variation caused to the conformational ensemble of Histatin 1 upon phosphorylation. The study applies molecular dynamics simulation, small-angle X-ray scattering, circular dichroism, bioinformatics tools, and neutron reflectometry. A multidimensional decomposition technique and its connection to clustering methods are also presented. It was observed that the phosphorylation of Histatin 1 profoundly shifts the conformational ensemble and may act as a molecular switch that facilitates tooth enamel binding. Observations are provided on the killing mechanisms of Histatins concerning self-association and membrane rupturing.
富组蛋白是一类多功能的、富含阳离子组氨酸的唾液肽家族。其中最具代表性的是富组蛋白1、富组蛋白3和富组蛋白5。尽管这三个成员在一级结构上有相当大的相似性，但已知它们具有不同的抗菌特性和愈合能力。本研究旨在对富组蛋白1、富组蛋白3和富组蛋白5进行详细的结构比较，并深入研究富组蛋白1磷酸化后其构象集合所产生的变化。该研究应用了分子动力学模拟、小角X射线散射、圆二色性、生物信息学工具和中子反射测量法。还介绍了一种多维分解技术及其与聚类方法的联系。研究发现，富组蛋白1的磷酸化会深刻改变其构象集合，并可能作为一种分子开关促进与牙釉质结合。文中还提供了关于富组蛋白自聚集和膜破裂的杀伤机制观察结果。
