Structure and Function of Membrane-Associated Peptides and Proteins

膜相关肽和蛋白质的结构和功能

• 批准号: 240795-2012
• 负责人: Straus, Suzana
• 金额: $ 4.01万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=570618
• 关键词: Structure; Function; Membrane; Associated; Peptides

Every cell is enveloped by a membrane, as are the various compartments within it. Therefore most biological processes either occur at or require transit through a membrane. Indeed, ca. 33% of all proteins are membrane associated. Despite their importance, however, relatively little is known about the 3D architecture of membrane proteins. Knowledge of protein structure is needed to understand function. The goal of our research is to study the interplay between protein structure and function in biological membranes. Despite the many challenges associated with working with membrane proteins (e.g. producing large amounts, limitations of the methods, etc.), we have made great strides in this area by studying biologically & pharmaceutically important biomolecules in their native lipid environment. We investigate 4 classes of proteins in biologically relevant lipids, using a wide range of biophysical methods: 1) ANTIMICROBIAL PEPTIDES: The rise of highly resistant "superbugs" imposes significant health and economic costs throughout the world. We are developing new sustainable antibiotics, by investigating the mechanisms of action of different types of bactericidal agents, both as free compounds and in implants. 2) VIRAL PROTEINS: Human Herpes Virus type 6 (HHV6) and type 7 (HHV7) are two viruses that have been found to be associated with Multiple Sclerosis (MS) and immunodeficiency-related diseases. We study the U24 membrane protein to determine how it may be linked to MS by tricking the body into attacking itself. 3) PHAGE COAT PROTEINS: How biological macromolecules insert into membranes in order to form large assemblies and to carry out highly specific functions is very poorly understood. We study the structure of filamentous bacteriophage proteins and their association to learn about these fundamental processes. 4) FUSION PEPTIDES: Viral fusion proteins contain short segments named fusion peptides (FP), which play a vital role in the entry of viruses into cells. We work on FPs from viruses related to West Nile Virus to determine how the structure relates to viral entry.

每一个细胞都被膜包裹着，就像它里面的各个隔间一样。因此，大多数生物过程要么发生在膜上，要么需要穿过膜。事实上，CA。33%的蛋白质是膜相关的。然而，尽管它们很重要，但对膜蛋白的3D结构知之甚少。了解蛋白质的结构是理解其功能的必要条件。 我们的研究目标是研究生物膜中蛋白质结构和功能之间的相互作用。尽管与膜蛋白的工作相关的许多挑战（例如产生大量、方法的限制等），通过研究生物学和药学上重要的生物分子在其天然脂质环境中的作用，我们在这一领域取得了长足的进步。我们使用广泛的生物物理方法研究了生物相关脂质中的4类蛋白质： 1)抗微生物肽：高度耐药的“超级细菌”的出现在全世界造成了巨大的健康和经济成本。我们正在开发新的可持续抗生素，通过研究不同类型的杀菌剂的作用机制，包括游离化合物和植入物。 2)病毒蛋白：人类疱疹病毒6型（HHV6）和7型（HHV7）是已发现与多发性硬化症（MS）和免疫缺陷相关疾病相关的两种病毒。我们研究了U24膜蛋白，以确定它如何通过欺骗身体攻击自己而与MS联系起来。 3)噬菌体包被蛋白：生物大分子是如何插入膜中以形成大的组装体并执行高度特异性的功能的，人们对此知之甚少。我们研究丝状噬菌体蛋白质的结构和它们的关联，以了解这些基本过程。 4)融合肽：病毒融合蛋白含有称为融合肽（FP）的短片段，其在病毒进入细胞中起重要作用。我们研究了与西尼罗河病毒相关的病毒的FP，以确定其结构与病毒进入的关系。