蛋白质动态结构影响混合膜脂相行为的研究

项目名称： 蛋白质动态结构影响混合膜脂相行为的研究

项目编号： No.21273130

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 尉志武

作者单位： 清华大学

项目金额： 84万元

中文摘要： 生物膜是细胞的重要组成部分、与生命活动紧密相关。脂筏是细胞膜上的一类有序微区结构，在细胞粘连、细胞凋亡、细胞迁移、信号转导等众多过程中起到重要作用。本项目以此为背景通过多种技术结合的手段，研究蛋白质对膜脂相行为的影响。选择的双组分膜脂体系（磷脂DPPC-胆固醇、糖脂GM3-胆固醇、磷脂DOPG-DPPC）在一定条件下都可以形成有序结构微区。本项目将研究多种蛋白质（溶菌酶、牛血清白蛋白、α-糜蛋白酶、γ-球蛋白等）在天然态、变性态、特别是解折叠过程中对混合膜脂体系相行为的影响，研究朊蛋白多肽PrP106-126及其修饰物在糖脂GM3-胆固醇体系液态有序相和液晶相中的分配及其对膜脂相行为的影响，揭示蛋白质结构及其变化过程对脂膜相行为的影响规律，确定作用位点，建立蛋白影响脂筏的作用模型。同时，本课题也将研究所选膜脂体系在相变过程中的区域协同性以及膜脂对蛋白质解折叠和聚集行为的影响规律。

中文关键词： 蛋白；动态结构；磷脂；相行为；

英文摘要： Biomembranes are important constituents of living cells. They are closely related to life activities. Lipid rafts are highly ordered structural domains in biomembranes, playing important roles in cellular connection, apoptosis, transportation, signal transduction, and so on. Taking this as background, we propose to investigate the modulation effect of proteins on the phase behavior of membrane lipids by means of various physical techniques. The selected binary lipid systems, DPPC-cholesterol, GM3-cholesterol, and DOPG-DPPC, can all form ordered microdomains under certain conditions. We will study the effects of a number of proteins such as lysozyme, BSA, α-chymotrypsin, and γ-globulin, in the native or unfolded states on the phase behavior. Particular attention will be paid on the effect of the dynamic structures of proteins during their unfolding processes on the lipid behavior. Interaction sites will be located and models on the membrane-proteins interactions will be established. In the meantime, we will also pay some attention on the regional cooperativity of the concerned lipids during phase transitions and the effect of the lipids on the unfolding and aggregation of the proteins.

英文关键词： Protein；Dynamic structure；phospholipid；Phase behaviour；