Heimburg-Molinaro Jamie, Mehta Akul Y, Tilton Catherine A, Cummings Richard D
Department of Surgery Beth Israel Deaconess Medical Center, National Center for Functional Glycomics (NCFG), Harvard Medical School, Boston, Massachusetts, USA.
Department of Surgery Beth Israel Deaconess Medical Center, National Center for Functional Glycomics (NCFG), Harvard Medical School, Boston, Massachusetts, USA.
Mol Cell Proteomics. 2024 Nov;23(11):100844. doi: 10.1016/j.mcpro.2024.100844. Epub 2024 Sep 21.
Glycans linked to proteins and lipids and also occurring in free forms have many functions, and these are partly elicited through specific interactions with glycan-binding proteins (GBPs). These include lectins, adhesins, toxins, hemagglutinins, growth factors, and enzymes, but antibodies can also bind glycans. While humans and other animals generate a vast repertoire of GBPs and different glycans in their glycomes, other organisms, including phage, microbes, protozoans, fungi, and plants also express glycans and GBPs, and these can also interact with their host glycans. This can be termed the protein-glycan interactome, and in nature is likely to be vast, but is so far very poorly described. Understanding the breadth of the protein-glycan interactome is also a key to unlocking our understanding of infectious diseases involving glycans, and immunology associated with antibodies binding to glycans. A key technological advance in this area has been the development of glycan microarrays. This is a display technology in which minute quantities of glycans are attached to the surfaces of slides or beads. This allows the arrayed glycans to be interrogated by GBPs and antibodies in a relatively high throughput approach, in which a protein may bind to one or more distinct glycans. Such binding can lead to novel insights and hypotheses regarding both the function of the GBP, the specificity of an antibody and the function of the glycan within the context of the protein-glycan interactome. This article focuses on the types of glycan microarray technologies currently available to study animal glycobiology and examples of breakthroughs aided by these technologies.
与蛋白质和脂质相连以及以游离形式存在的聚糖具有多种功能,其中部分功能是通过与聚糖结合蛋白(GBP)的特异性相互作用引发的。这些GBP包括凝集素、黏附素、毒素、血凝素、生长因子和酶,但抗体也能结合聚糖。虽然人类和其他动物在其糖组中产生了大量的GBP和不同的聚糖,但其他生物体,包括噬菌体、微生物、原生动物、真菌和植物也表达聚糖和GBP,并且这些也能与它们宿主的聚糖相互作用。这可以称为蛋白质 - 聚糖相互作用组,在自然界中其规模可能非常庞大,但迄今为止描述得非常少。了解蛋白质 - 聚糖相互作用组的广度也是解开我们对涉及聚糖的传染病以及与抗体结合聚糖相关的免疫学理解的关键。该领域的一项关键技术进步是聚糖微阵列的发展。这是一种展示技术,其中微量的聚糖附着在载玻片或珠子的表面。这使得排列好的聚糖能够通过GBP和抗体以相对高通量的方式进行检测,在这种方式中一种蛋白质可能与一种或多种不同的聚糖结合。这种结合能够带来关于GBP功能、抗体特异性以及在蛋白质 - 聚糖相互作用组背景下聚糖功能的新见解和假设。本文重点介绍目前可用于研究动物糖生物学的聚糖微阵列技术类型以及这些技术促成的突破实例。