Coeliac autoantibodies can enhance transamidating and inhibit GTPase activity of tissue transglutaminase:: Dependence on reaction environment and enzyme fitness
Coeliac autoantibodies can enhance transamidating and inhibit GTPase activity of tissue transglutaminase:: Dependence on reaction environment and enzyme fitness
复制标题
DOI：
10.1016/j.jaut.2006.03.002
复制
发表时间：
2006-06-01
影响因子：
12.8
通讯作者：
Fesus, Laszlo
中科院分区：
文献类型：
--
作者：
Kiraly, Robert;Vecsei, Zsofia;Fesus, Laszlo
组织转谷氨酰胺酶(TG2)自身抗体对TG2酶功能的修饰可能在肠道疾病的表现中起一定作用。我们的目的是通过系统的生化方法来评估腹腔自身抗体对TG2催化的反应的影响，以及与观察到的临床表现类型的关系。通过固体酪蛋白和固定化酪蛋白的胺掺入实验和紫外动力学实验表明，腹腔抗体对TG2的转酰胺化/脱酰胺化活性没有明显的抑制作用。相比之下，来自严重吸收不良患者的免疫球蛋白将反应速度提高到105.4-242.2%。这种激活作用是剂量依赖的，在固定化谷氨酰胺受体底物时最为明显，与酶的基础比活性和饮食处理呈负相关。自身抗体的TG2特异性部分也可以表现出类似的激活，在使用纤维连接蛋白结合的TG2从而模拟体内条件的转酰化活性分析中也可以证明。这些结果表明，腹腔抗体可以稳定酶的催化优势构象。在抗体存在的情况下，TG2的GTPase活性下降到67.0-73.4%，增加了抑制GTPase活性可能会影响细胞信号传递的可能性，以防腹水自身抗体到达细胞内隔室。(C)2006年，爱思唯尔有限公司出版。
Modification of the enzymatic functions of tissue transglutaminase (TG2) by anti-TG2 autoantibodies may play a role in manifestations of coeliac disease. Our aim was to evaluate the effect of coeliac autoantibodies on reactions catalysed by TG2 by a systematic biochemical approach, and in relation to observed clinical presentation type. Coeliac antibodies did not have significant inhibitory effect on transamidation/deamidation activity of TG2 as measured by amine-incorporation into solid and immobilised casein and by ultraviolet kinetic assay. In contrast, immunoglobulins from patients with severe malabsorption enhanced the reaction velocity to 105.4-242.2%. This activating effect was dose-dependent, most pronounced with immobilised glutamine-acceptor substrates, and correlated inversely with the basal specific activity of the enzyme and with dietary treatment. A similar activation could be demonstrated also with the TG2-specific fraction of autoantibodies and in transamidation activity assays which use fibronectin-bound TG2 and thereby mimic in vivo conditions. These results suggest that coeliac antibodies may stabilise the enzyme in a catalytically advantageous conformation. GTPase activity of TG2 decreased to 67.0-73.4% in the presence of antibodies raising the possibility that inhibition of GTPase activity may affect cellular signalling in case coeliac autoantibodies would reach intracellular compartments. (c) 2006 Published by Elsevier Ltd.