Xylosyl- and glucuronyltransferase functions of LARGE in α-dystroglycan modification are conserved in LARGE2.
Xylosyl- and glucuronyltransferase functions of LARGE in α-dystroglycan modification are conserved in LARGE2.
复制标题
DOI：
10.1093/glycob/cws152
复制
发表时间：
2013-03
期刊：
影响因子：
4.3
通讯作者：
Campbell KP
中科院分区：
文献类型：
--
作者：
Inamori K;Hara Y;Willer T;Anderson ME;Zhu Z;Yoshida-Moriguchi T;Campbell KP
大依赖修饰使α-三聚糖聚糖（α-DG）能够与其细胞外基质配体结合。在先天性和肢带性肌营养不良症中发现了LARGE基因和其他参与o -甘露糖基糖合成的基因突变，其特征是糖基化紊乱和α-DG配体结合亲和力降低。LARGE是一种双功能糖基转移酶，它交替转移木糖和葡萄糖醛酸，从而在α-DG上产生异多糖，使其与配体结合。尽管LARGE2（也被称为GYLTL1B）也被证明可以增强α-DG在培养细胞中的功能修饰，但其酶活性尚未被确定。在这里，我们报道了LARGE2也是一种双功能糖基转移酶，并将其与LARGE的性质进行了比较。通过高效液相色谱酶分析，我们证明了LARGE2与LARGE一样具有木糖基转移酶（yl- t）和葡萄糖醛基转移酶（GlcA-T）活性，以及聚合活性。然而，值得注意的是，LARGE2的yl- t和GlcA-T的pH最佳值彼此不同，也与LARGE不同。我们的研究结果表明，LARGE和LARGE2催化α-DG功能修饰的糖基化反应相同，但它们具有不同的生化性质。
LARGE-dependent modification enables α-dystroglycan (α-DG) to bind to its extracellular matrix ligands. Mutations in the LARGE gene and several others involved in O-mannosyl glycan synthesis have been identified in congenital and limb-girdle muscular dystrophies that are characterized by perturbed glycosylation and reduced ligand-binding affinity of α-DG. LARGE is a bifunctional glycosyltransferase that alternately transfers xylose and glucuronic acid, thereby generating the heteropolysaccharides on α-DG that confer its ligand binding. Although the LARGE paralog LARGE2 (also referred to as GYLTL1B) has likewise been shown to enhance the functional modification of α-DG in cultured cells, its enzymatic activities have not been identified. Here, we report that LARGE2 is also a bifunctional glycosyltransferase and compare its properties with those of LARGE. By means of a high-performance liquid chromatography-based enzymatic assay, we demonstrate that like LARGE, LARGE2 has xylosyltransferase (Xyl-T) and glucuronyltransferase (GlcA-T) activities, as well as polymerizing activity. Notably, however, the pH optima of the Xyl-T and GlcA-T of LARGE2 are distinct from one another and also from those of LARGE. Our results suggest that LARGE and LARGE2 catalyze the same glycosylation reactions for the functional modification of α-DG, but that they have different biochemical properties.
登录
查看更多内容
影响因子：
7.7
作者：
Senay, C;Lind, T;Kusche-Gullberg, M
通讯作者：
Kusche-Gullberg, M
DOI：
10.1016/s0304-4165(01)00147-7
发表时间：
2001-07-02
影响因子：
3
作者：
Pereboev, AV;Ahmed, N;Morris, GE
通讯作者：
Morris, GE
DOI：
10.1073/pnas.96.2.598
发表时间：
1999-01-19
影响因子：
11.1
作者：
Peyrard, M;Seroussi, E;Dumanski, JP
通讯作者：
Dumanski, JP
影响因子：
30.8
作者：
McCormick, C;Leduc, Y;Tufaro, F
通讯作者：
Tufaro, F
DOI：
10.1126/science.1214115
发表时间：
2012-01-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Inamori K;Yoshida-Moriguchi T;Hara Y;Anderson ME;Yu L;Campbell KP
通讯作者：
Campbell KP