The Dominating Role of N-Deacetylase/N-Sulfotransferase 1 in Forming Domain Structures in Heparan Sulfate
The Dominating Role of N-Deacetylase/N-Sulfotransferase 1 in Forming Domain Structures in Heparan Sulfate
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DOI：
10.1074/jbc.m111.224311
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发表时间：
2011-06-03
影响因子：
4.8
通讯作者：
Liu, Jian
中科院分区：
文献类型：
--
作者：
Sheng, Juzheng;Liu, Renpeng;Liu, Jian
硫酸乙酰肝素（HS）是一种高度硫酸化的多糖，参与从调节细胞生长到血液凝固的基本生理功能。HS含有称为N-S结构域的硫酸化结构域和称为N-Ac结构域的低硫酸化结构域。域结构的分布可能是由葡糖胺基N-脱乙酰基酶/N-磺基转移酶（NDST）的作用。在这里，我们试图确定使用模型底物和重组NDST蛋白的NDST的底物特异性。我们发现NDST-1以高度有序的方式进行修饰。该酶从非还原端向还原端连续硫酸化底物，产生具有N-磺基葡糖胺残基簇的产物。此外，预先存在的N-磺基葡糖胺残基阻止NDST-1在直接位于非还原末端的残基处的作用，从而允许形成N-Ac结构域。我们的研究结果提供了长期寻求的证据，了解形成的硫酸化与非硫酸化结构域的HS分离的细胞和组织。该研究表明NDST-1在绘制HS硫酸化模式中的调节作用。
Heparan sulfate (HS) is a highly sulfated polysaccharide participated in essential physiological functions from regulating cell growth to blood coagulation. HS contains sulfated domains known as N-S domains and low sulfate domains known as N-Ac domains. The distribution of the domain structures is likely governed by the action of glucosaminyl N-deacetylase/N-sulfotransferase (NDST). Here, we sought to determine the substrate specificity of NDST using model substrates and recombinant NDST protein. We discovered that NDST-1 carries out the modification in a highly ordered fashion. The enzyme sulfates the substrate from the nonreducing end toward the reducing end consecutively, leading to the product with a cluster of N-sulfo glucosamine residues. Furthermore, a preexisting N-sulfo glucosamine residue prevents the action of NDST-1 at the residues immediately located at the nonreducing end, allowing the formation of an N-Ac domain. Our results provide the long sought evidence for understanding the formation of sulfated versus nonsulfated domains in the HS isolated from cells and tissues. The study demonstrates the regulating role of NDST-1 in mapping the sulfation patterns of HS.