Synthetic glycopeptides reveal specific binding pattern and conformational change at O-mannosylated position of α-dystroglycan by POMGnT1 catalyzed GlcNAc modification
Synthetic glycopeptides reveal specific binding pattern and conformational change at O-mannosylated position of α-dystroglycan by POMGnT1 catalyzed GlcNAc modification
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DOI：
10.1016/j.bmc.2019.05.008
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发表时间：
2019-07-01
影响因子：
3.5
通讯作者：
Nishimura, Shin-Ichiro
中科院分区：
文献类型：
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作者：
Hinou, Hiroshi;Kikuchi, Seiya;Nishimura, Shin-Ichiro
利用α -异糖甘氨酸片段（372）TRGAIIQTPTLGPIQPTRV（390）的核心M1糖型集中库，研究了蛋白o -连接甘露糖β 1,2- n -乙酰氨基葡萄糖转移酶1 （POMGnT1）催化的核心M1型聚糖修饰的结构和功能效应。微阵列荧光辅助系统显示了植物凝集素的特异性结合模式，可以区分库中M1核心聚糖的聚糖结构。对不同长度的o -甘露糖基化聚糖合成的糖肽进行核磁共振对比分析，发现随着核心M1双糖的形成，肽主链的构象发生了变化。在哺乳动物中发现的蛋白结合糖残基中唯一的1,2- o修饰形式M1的位阻引起了构象的改变，但没有发现甘氨酸-氨基酸或氨基酸间的远程NOE信号。
Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose beta 1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an alpha-dystroglycan fragment, (372)TRGAIIQTPTLGPIQPTRV(390). Evanescent-field fluorescence-assisted microarray system illuminated the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library. The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation. No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.