Dwek R A, Lellouch A C, Wormald M R
Department of Biochemistry, University of Oxford, UK.
J Anat. 1995 Oct;187 ( Pt 2)(Pt 2):279-92.
Immunoglobulin G (IgG) is glycosylated in both the Fc and the Fab regions of the protein with a heterogeneous ensemble of structures (glycoforms) that is both highly reproducible (i.e. nonrandom) and site specific. In normal IgG, the 2 highly conserved oligosaccharides of the Fc region are found buried between the CH2 domains, forming specific protein-saccharide interactions with the Fc protein surface. One of the functions attributed to the Fc oligosaccharides of normal IgG is to maintain the conformational arrangements of the Fc domains as well as the hinge regions. These structural features are necessary for Fc effector functions such as Clq and monocyte binding. A hallmark of rheumatoid arthritis (RA) patients is a dramatic increase in the presence of serum IgG containing Fc oligosaccharides lacking an outer arm galactose residue (termed 'G0' glycoforms). The increased level of G0 has been shown to be directly related to the pathogenesis of RA. Nuclear magnetic resonance relaxation studies of the Fc region from normal and RA IgG, as well as examination of x-ray structures, show that the G0 oligosaccharides have an increased mobility resulting from the loss of binding between the G0 oligosaccharide and the Fc protein surface. From these observations it follows that regions of the protein surface that are normally covered by the oligosaccharide are revealed. The newly accessible protein surface could have lectin-like activity and also be inherently antigenic. In addition, the more mobile G0 oligosaccharide can be recognised by mannose binding protein. As the mannose binding protein can activate complement, and the Fc oligosaccharide would not normally be accessible to protein recognition, this finding might suggest a specific role for the G0 glycoform in inflammation when the appropriate IgG glycoforms are clustered.
免疫球蛋白G（IgG）在蛋白质的Fc和Fab区域均被糖基化，其结构（糖型）的异质集合具有高度可重复性（即非随机）且具有位点特异性。在正常IgG中，Fc区域的2个高度保守的寡糖位于CH2结构域之间，与Fc蛋白表面形成特定的蛋白质-糖相互作用。正常IgG的Fc寡糖的功能之一是维持Fc结构域以及铰链区的构象排列。这些结构特征对于Fc效应功能（如Clq和单核细胞结合）是必需的。类风湿性关节炎（RA）患者的一个标志是含有缺乏外臂半乳糖残基的Fc寡糖的血清IgG（称为“G0”糖型）的存在显著增加。已证明G0水平的升高与RA的发病机制直接相关。对正常和RA IgG的Fc区域进行核磁共振弛豫研究以及对X射线结构的检查表明，G0寡糖由于G0寡糖与Fc蛋白表面之间结合的丧失而具有增加的流动性。从这些观察结果可以推断，通常被寡糖覆盖的蛋白质表面区域被暴露出来。新暴露的蛋白质表面可能具有凝集素样活性，并且本身也具有抗原性。此外，流动性更强的G0寡糖可以被甘露糖结合蛋白识别。由于甘露糖结合蛋白可以激活补体，而Fc寡糖通常不会被蛋白质识别，这一发现可能表明当适当的IgG糖型聚集时，G0糖型在炎症中具有特定作用。
