Membrane - protein interactions

生物膜中蛋白质的结构和功能强烈依赖于蛋白质-脂质相互作用，蛋白质-脂质相互作用实现并控制重要的转运功能、信号转导、病理发生和细胞与细胞的通讯。这是该项目的目的，以表征与生物膜的脂质成分的膜蛋白的相互作用。为了实现这一目标，蛋白质结构和膜脂质组成以及温度和共溶剂的化学势将在化学定义的蛋白脂质体中变化，并分析这些参数对膜生物物理性质和膜蛋白功能的影响。来自乳酸乳球菌的转运蛋白LmrP，一种多药耐药（MDR）转运蛋白，和一种组氨酸激酶， 以罗伊氏乳杆菌的膜结合调节蛋白为模型系统。该提案的主要目标是确定蛋白质功能，与德国多特蒙德大学罗兰温特博士的现有合作将补充该提案，以确定蛋白质结构的改变。在模型系统的初步工作的基础上，设想了以下长期目标：·完整膜蛋白的结构和功能对生物膜的生物物理性质的依赖性。·了解生物膜作为信号转导级联中的初始试剂的作用及其作为环境中化学和物理变化的“传感器”的相关性。·开发基于信号转导级联和抗性机制的靶向干预的食品中细菌控制新策略。

The structure and function of proteins in biological membranes is stongly dependent on protein-lipid interactions, which enable and control vital transport functions, signal transduction, pathegenesis, and cell to cell communication. It is the aim of this project to characterize the interactions of integral membrane proteins with the lipid components of biological membranes. To achieve this aim, protein structure and membrane lipid composition as well as temperature and chemical potential of co-solvents will be varied in chemically defined proteoliposomes, and the effect of these parameters on membrane biophysical properties and the function of membrane proteins will be analysed. The transport protein LmrP from Lactococcus lactis, an multi-drug-resistance (MDR) transporter, and a histidine kinase, a   membrane bound regulagory protein in Lactobacillus reuteri will be used as model system. The primary objective of this proposal is the determination of protein function, existing collaborations with Dr. Roland Winter, Universität Dortmund, Germany, will complement this proposal to determine alterations in protein structure. On the basis of the initial work with the model systems, the following long-term objecives are envisaged: · Dependence of structure and function of integral membrane proteins on biophysical properties of biological membranes. · Knowledge on the role of biological membranes as initial agents in signal transduction cascades and their relevance as "sensors" for chemical and physical changes in the enironment. · Development of new strategies for the control of bacteria in foods based on targeted intervention with signal transduction cascades, and resistance mechanisms.