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，这种相互作用能够实现和控制重要的运输功能、信号转导、发病机制和细胞间通讯。这是本项目的目的是表征整体膜蛋白与生物膜的脂质成分的相互作用。为了实现这一目标，将在化学定义的蛋白脂质体中改变蛋白质结构和膜脂组成以及共溶剂的温度和化学势，并分析这些参数对膜生物物理性质和膜蛋白功能的影响。以乳球菌（Lactococcus lactis）多药耐药转运蛋白LmrP和罗伊氏乳杆菌（Lactobacillus reuteri）膜结合调节蛋白组氨酸激酶（histidine kinase）为模型系统。该提案的主要目标是确定蛋白质功能，目前与德国多特蒙德（Universität Dortmund）的Roland Winter博士的合作将补充该提案，以确定蛋白质结构的改变。在模型系统初步工作的基础上，设想了以下长期目标：·整体膜蛋白的结构和功能依赖于生物膜的生物物理特性。·了解生物膜在信号转导级联中的初始作用，以及它们作为环境中化学和物理变化的“传感器”的相关性。·基于信号转导级联的靶向干预和耐药机制，开发控制食品中细菌的新策略。

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.