FASEB Conference: Lipid Modifications of Proteins to be held on August 6-11, 2000 in Copper Mountain, CO

FASEB 会议：蛋白质脂质修饰将于 2000 年 8 月 6 日至 11 日在科罗拉多州铜山举行

• 批准号: 0076692
• 负责人: Maurine Linder
• 金额: $ 0.5万
• 依托单位: Federation of Amer Societies For Exper Biology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0076692&HistoricalAwards=false
• 关键词: FASEB; Conference; Lipid; Modifications; Proteins

This project seeks partial support for the Federation of American Societies of Experimental Biology (FASEB) conference on "Lipid Modifications of Proteins" to be held from August 6 to August 11, 2000 at Copper Mountain, Colorado. This will be a state-of-the-art exploration of the structure and function of acylation, prenylation, and GPI-anchorage, the three major forms of lipid modification of proteins in eukaryotic cells, and will provide a unique opportunity for workers in these separate but related fields to exchange ideas and insights. Lipid modification of proteins is an extremely active field. The focus of research in this area has broadened in the past few years from an earlier focus on identification of lipid-modified proteins and structural studies, to include elucidation of the physiological role of the lipid group. Outlined below are the major themes of the meeting. Signaling. Surprisingly high proportions of lipid-linked proteins are key players in cellular signaling pathways. These include Ras, Src-family tyrosine kinases, heterotrimeric G proteins, and 7- transmembrane spanning hormone receptors. In virtually all cases, the lipid modifications are required for function. This focuses attention on the specific role of these lipid groups in cellular physiology. All lipid modifications can allow association of otherwise hydrophilic proteins with membranes. Why are there different lipid modifications? What do they have in common, and how do they differ? Recent results on Ras show that modification of the same protein with different lipids can substantially alter function. New insights into these and other questions can be best answered by discussion between people who focus on individual modifications. This is one of the most important goals of this meeting. Membrane rafts. An important function of both GPI anchorage and acylation is to target proteins to cholesterol and sphingolipid-rich membrane domains or rafts. The finding that a number of cellular signaling events occur in these domains is an exciting development of the past two years, and has attracted a great deal of interest. Structure and function of rafts, and function of lipid-linked proteins in them, is another theme of the conference. Related to this theme are the importance of cholesterol in the biogenesis and maintenance of membrane rafts and its recently discovered role as a post-translational modification of the cell surface signaling molecule, hedgehog. Therapeutic applications of inhibiting lipid modifications. A third theme of this meeting will explore how inhibition of lipid modification can be used as a highly effective strategy in fighting disease. This effort can be divided in two major subclasses. The first is the use of farnesyl transferase inhibitors to blunt the function of activated Ras. The second target is infectious disease caused by unicellular eukaryotic pathogens such as Trypanosoma, Leishmania, and Plasmodium. Most of these organisms express extremely high levels of GPI-anchored proteins. Synthesis of these complex structures by a multistep pathway requires a number of enzymes, some of which are specific to the pathogens and are not shared by mammalian hosts. These are key targets for drug design, an avenue that is being actively pursued. Pathogen-specific features of myristoylation and prenylation are being targeted similarly. Lipid modification and membrane targeting. All lipid modifications increase protein hydrophobicity, and all lipid modifications can target lipidated proteins to membranes. But how are lipidated proteins targeted to different membranes? The specificity of membrane targeting of acylated and prenylated proteins is one of the most active areas of current research. The emerging picture that acylated and prenylated proteins can follow complicated pathways through cells following synthesis will be explored. Lipid-modified proteins are integral players in the cellular processes of signal transduction, membrane and protein trafficking, cellular proliferation and differentiation. The disciplines of cell biology, genetics, biochemistry, and biophysics are all used to understand the biology of protein lipidation. This meeting provides the opportunity to integrate the information derived from these approaches into a more coherent picture of how lipid modifications contribute to protein function.

该项目寻求对美国实验生物学学会联合会（FASEB）将于2000年8月6日至8月11日在科罗拉多铜山举行的“蛋白质的脂质修饰”会议的部分支持。这将是对酰化、异戊烯化和GPI锚定的结构和功能的最新探索，这是真核细胞中蛋白质脂质修饰的三种主要形式，并将为这些独立但相关领域的工作者提供一个独特的机会来交流思想和见解。蛋白质的脂质修饰是一个非常活跃的领域。在过去的几年中，这一领域的研究重点已经从早期的重点确定脂质修饰的蛋白质和结构研究，包括阐明脂质组的生理作用。会议的主要议题概述如下。发信号令人惊讶的是，高比例的脂质连接蛋白是细胞信号传导途径的关键参与者。这些包括Ras、Src家族酪氨酸激酶、异源三聚体G蛋白和7跨膜激素受体。几乎在所有情况下，脂质修饰都是功能所必需的。这将注意力集中在这些脂质基团在细胞生理学中的特定作用上。所有的脂质修饰都可以使亲水性蛋白质与膜结合。为什么有不同的脂质修饰？它们有什么共同点，又有什么不同？Ras的最新研究结果表明，用不同的脂质修饰相同的蛋白质可以显著改变功能。对这些和其他问题的新见解可以通过专注于个人修改的人之间的讨论来最好地回答。这是本次会议最重要的目标之一。膜筏。GPI锚定和酰化的一个重要功能是将蛋白质靶向胆固醇和鞘脂丰富的膜结构域或筏。在这些领域中发生的许多细胞信号事件的发现是过去两年令人兴奋的发展，并引起了极大的兴趣。筏的结构和功能，以及其中的脂质连接蛋白的功能，是会议的另一个主题。与这一主题相关的是胆固醇在膜筏的生物发生和维持中的重要性及其最近发现的作为细胞表面信号分子hedgehog的翻译后修饰的作用。抑制脂质修饰的治疗应用。本次会议的第三个主题将探讨如何抑制脂质修饰可以作为一个非常有效的战略，在战斗中的疾病。这项工作可以分为两个主要的子类。第一种是使用法尼基转移酶抑制剂来钝化活化的Ras的功能。第二个目标是由单细胞真核病原体如锥虫、利什曼原虫和疟原虫引起的感染性疾病。这些生物体中的大多数表达极高水平的GPI锚定蛋白。通过多步途径合成这些复杂结构需要许多酶，其中一些酶对病原体是特异性的，并且不为哺乳动物宿主所共有。这些都是药物设计的关键目标，这是一个正在积极探索的途径。豆蔻酰化和异戊烯化的病原体特异性特征被类似地靶向。脂质修饰和膜靶向。所有脂质修饰都增加蛋白质的疏水性，并且所有脂质修饰都可以将脂化蛋白质靶向膜。但是脂化蛋白质是如何靶向不同的细胞膜的呢？酰化和异戊烯化蛋白的膜靶向特异性是当前研究的最活跃领域之一。将探索新出现的图像，即酰化和异戊烯化蛋白质在合成后可以沿着复杂的途径通过细胞。脂质修饰的蛋白质在信号转导、膜和蛋白质运输、细胞增殖和分化的细胞过程中是不可或缺的参与者。细胞生物学、遗传学、生物化学和生物物理学的学科都用于理解蛋白质脂化的生物学。这次会议提供了一个机会，将这些方法获得的信息整合到一个更连贯的画面，脂质修饰如何有助于蛋白质功能。