Structure and Function of Membrane-Associated Peptides and Proteins

每个细胞都被一层膜包裹着，它里面的各个隔间也是如此。因此，大多数生物过程要么发生在膜上，要么需要通过膜。事实上，约33%的蛋白质与膜相关。然而，尽管它们很重要，但人们对膜蛋白的3D结构知之甚少。了解蛋白质的功能需要了解蛋白质结构的知识。 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，大量生产，方法的局限性，等等)，我们已经在这一领域取得了长足的进步，通过研究在其天然脂环境中具有生物和药学意义的重要生物分子。我们使用广泛的生物物理方法研究了4类与生物相关的脂质中的蛋白质： 1)抗菌肽：高度耐药的“超级细菌”的兴起在世界各地造成了巨大的健康和经济代价。我们正在开发新的可持续的抗生素，通过研究不同类型的杀菌剂作为游离化合物和植入物的作用机制。 2)病毒蛋白：人类疱疹病毒6型(HHV6)和7型(HHV7)是两种已被发现与多发性硬化症(MS)和免疫缺陷相关疾病有关的病毒。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多发性硬化症联系在一起。 3)噬菌体外壳蛋白：生物大分子如何插入细胞膜以形成大的集合并执行高度特定的功能目前还知之甚少。我们研究丝状噬菌体蛋白的结构及其相互作用，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，在病毒进入细胞的过程中起着至关重要的作用。我们对与西尼罗河病毒相关的病毒的FP进行研究，以确定其结构与病毒进入的关系。

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.