Investigations Into the Regulation of Plasticity of O-Linked Glycosylation and its Functional Significance

O-联糖基化可塑性调控及其功能意义的研究

• 批准号: 2656420
• 金额: --
• 依托单位: Oxford Brookes University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2656420
• 关键词: Investigations; Into; Regulation; Plasticity; Linked

Glycosylation is a co-ordinated process where single sugars or sugar chains, called glycans, are added to proteins by enzymes to form glycoproteins. It is an important and abundant form of protein modification and approximately half of all proteins in humans are glycosylated. There are various types of glycosylation however, this project will focus on O-linked glycosylation. The most common form of O-linked glycosylation is initiated by the addition of a sugar residue called N-acetylgalactosamine (GalNAc) to either a Serine (Ser) or Threonine (Thr) amino acid within a protein, to form the Tn antigen. In normal healthy cells this initial structure is then further elaborated to form eight core structures. When alterations in O-linked glycosylation occur, such as failure in O-glycan chain extension it exposes the usually cryptic Tn antigen. The surface of cells are decorated with O-linked glycoproteins which are implicit in essential biological functions, these range from metabolic to structural and physical functions. Despite this biological significance, the O-linked glycosylation repertoire of a cell, itsfunctionality and the factors regulating it are still poorly understood. This project will therefore investigate the regulation of plasticity demonstrated in O-linked glycans by exploring and manipulating potential underlying regulatory mechanisms. It will also investigate the functional significance of this plasticity by exploring the relationship between O-linked glycosylation status and functionality in processes such as cell-cell adhesion, cell invasion and cell migratory capability.

糖基化是一个协调的过程，单糖或糖链，被称为聚糖，通过酶添加到蛋白质中形成糖蛋白。它是一种重要而丰富的蛋白质修饰形式，大约一半的人类蛋白质是糖基化的。有各种类型的糖基化，然而，本项目将重点关注o链糖基化。o链糖基化最常见的形式是在蛋白质中添加一种叫做n -乙酰半乳糖胺（GalNAc）的糖残基，使其与丝氨酸（Ser）或苏氨酸（Thr）氨基酸结合，形成Tn抗原。在正常的健康细胞中，这种初始结构随后进一步发展形成八个核心结构。当o -链糖基化发生改变时，例如o -聚糖链延伸失败时，通常会暴露出隐藏的Tn抗原。细胞表面装饰着o -连接糖蛋白，这些糖蛋白隐含在基本的生物功能中，从代谢到结构和物理功能。尽管具有这种生物学意义，但细胞的o链糖基化库、其功能和调节它的因素仍然知之甚少。因此，该项目将通过探索和操纵潜在的潜在调节机制来研究o链聚糖中可塑性的调节。本研究还将通过探索o链糖基化状态与细胞粘附、细胞侵袭和细胞迁移能力等过程中的功能之间的关系来研究这种可塑性的功能意义。