Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, Sweden.
Institut Curie, Université PSL, Paris, France.
Biol Cell. 2022 Jun;114(6):160-176. doi: 10.1111/boc.202200017. Epub 2022 Mar 31.
Like most other cell surface proteins, α β integrin is glycosylated, which is required for its various activities in ways that mostly remain to be determined.
Here, we have established the first comprehensive site-specific glycan map of α β integrin that was purified from a natural source, that is, rat liver. This analysis revealed striking site selective variations in glycan composition. Complex bi, tri, or tetraantennary N-glycans were predominant at various proportions at most potential N-glycosylation sites. A few of these sites were nonglycosylated or contained high mannose or hybrid glycans, indicating that early N-glycan processing was hindered. Almost all complex N-glycans had fully galactosylated and sialylated antennae. Moderate levels of core fucosylation and high levels of O-acetylation of NeuAc residues were observed at certain sites. An O-linked HexNAc was found in an EGF-like domain of β integrin. The extensive glycan information that results from our study was projected onto a map of α β integrin that was obtained by homology modeling. We have used this model for the discussion of how glycosylation might be used in the functional cycle of α β integrin. A striking example concerns the involvement of glycan-binding galectins in the regulation of the molecular homeostasis of glycoproteins at the cell surface through the formation of lattices or endocytic pits according to the glycolipid-lectin (GL-Lect) hypothesis.
We expect that the glycoproteomics data of the current study will serve as a resource for the exploration of structural mechanisms by which glycans control α β integrin activity and endocytic trafficking.
Glycosylation of α β integrin has been implicated in multiple aspects of integrin function and structure. Yet, detailed knowledge of its glycosylation, notably the specific sites of glycosylation, is lacking. Furthermore, the α β integrin preparation that was analyzed here is from a natural source, which is of importance as there is not a lot of literature in the field about the glycosylation of "native" glycoproteins.
与大多数其他细胞表面蛋白一样，αβ 整合素发生糖基化，这对于其各种活性是必需的，但具体方式仍有待确定。
在这里，我们建立了第一个从天然来源（即大鼠肝脏）纯化的 αβ 整合素的综合、定点糖基图谱。该分析揭示了糖基组成的显著的位点选择性变化。大多数潜在的 N-糖基化位点以各种比例主要存在复杂的双、三或四天线 N-聚糖。其中一些位点未发生糖基化，或含有高甘露糖或杂合聚糖，表明早期 N-聚糖加工受到阻碍。几乎所有的复合 N-聚糖都具有完全半乳糖化和唾液酸化的天线。在某些位点观察到中等程度的核心岩藻糖基化和 NeuAc 残基的高乙酰化水平。在 β 整合素的一个 EGF 样结构域中发现了一个 O-连接的 HexNAc。我们的研究产生的广泛糖基化信息被投射到通过同源建模获得的 αβ 整合素图谱上。我们使用该模型讨论了糖基化如何在 αβ 整合素的功能循环中发挥作用。一个引人注目的例子是糖基结合半乳糖凝集素根据糖脂-凝集素（GL-Lect）假说参与通过形成晶格或内陷坑来调节细胞表面糖蛋白的分子动态平衡。
我们期望当前研究的糖蛋白质组学数据将成为探索糖基控制 αβ 整合素活性和内吞作用的结构机制的资源。
αβ 整合素的糖基化已被涉及整合素功能和结构的多个方面。然而，其糖基化的详细知识，特别是糖基化的特定位点，仍然缺乏。此外，在这里分析的 αβ 整合素制剂来自天然来源，这很重要，因为在该领域关于“天然”糖蛋白的糖基化的文献并不多。
