Uncovering the Relationship between Sulphation Patterns and Conformation of Iduronic Acid in Heparan Sulphate.

Uncovering the Relationship between Sulphation Patterns and Conformation of Iduronic Acid in Heparan Sulphate.
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DOI:
10.1038/srep29602
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发表时间:
2016-07-14
期刊:
影响因子:
4.6
通讯作者:
Liu J
Liu J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hsieh PH;Thieker DF;Guerrini M;Woods RJ;Liu J

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L-艾杜糖醛酸(IdoA)残基是硫酸乙酰肝素多糖中具有重要生物学功能的结构组分。IdoA的吡喃糖环存在于1C 4-椅型、2SO-斜船型中,并且较少地存在于4C 1-椅型构象中。本文利用核磁共振技术分析了八种六糖中IdoA残基的构象。数据表明IdoA的构象与周围糖残基中的硫酸化之间的相关性。对于2-O-磺基IdoA残基,相邻残基上的高度硫酸化驱动环动力学朝向2SO-斜船构象。相反,当邻近的残基高度硫酸化时,非硫酸化的IdoA残基被推向1C 4-椅型构象异构体。我们的数据表明,IdoA的构象是由附近的硫酸乙酰肝素的生物合成途径,这是遗传控制的硫酸化模式。
The L-iduronic acid (IdoA) residue is a critically important structural component in heparan sulphate polysaccharide for the biological functions. The pyranose ring of IdoA is present in 1C4-chair, 2SO-skew boat, and less frequently, in 4C1-chair conformations. Here, we analyzed the conformation of IdoA residue in eight hexasaccharides by NMR. The data demonstrate a correlation between the conformation of IdoA and sulphations in the surrounding saccharide residues. For the 2-O-sulpho IdoA residue, a high degree of sulphation on neighboring residues drives ring dynamics towards the 2SO-skew boat conformer. In contrast, the nonsulphated IdoA residue is pushed towards the 1C4-chair conformer when the neighboring residues are highly sulphated. Our data suggest that the conformation of IdoA is regulated by the sulphation pattern of nearby saccharides that is genetically controlled by the heparan sulphate biosynthetic pathway.