Conformational studies on the MUC1 tandem repeat glycopeptides: implication for the enzymatic O-glycosylation of the mucin protein core
Conformational studies on the MUC1 tandem repeat glycopeptides: implication for the enzymatic O-glycosylation of the mucin protein core
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DOI：
10.1093/glycob/cwg109
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发表时间：
2003-12-01
期刊：
影响因子：
4.3
通讯作者：
Sherman, S
中科院分区：
文献类型：
--
作者：
Kinarsky, L;Suryanarayanan, G;Sherman, S
MUC1 蛋白核心的串联重复是 O-糖基化的主要位点，由多种多肽 GalNAc 转移酶催化。为了定义有助于受体底物效率的肽底物的结构特征，来自 MUC1 蛋白核心的 21 残基肽 AHGVTSAPDTRPAPGSTAPA (AHG21) 和四种亚型的溶液结构，在相应的 Thr 残基上用 α-N-乙酰半乳糖胺糖基化，AHG21 (T5)、AHG21 (T10)、AHG21 (T17) 和 AHG21 （T5，T17），通过核磁共振波谱和计算方法进行了研究。 NMR 研究表明，糖附着影响糖基化 Thr 残基附近肽主链的构象平衡。 VTSA、DTR 和 GSTA 片段（包括 GalNAc-T1、-T2 和 -T4 转移酶催化的所有潜在糖基化位点）内非糖基化和糖基化对应物的低能构象的聚类表明，糖基化肽表现出不同的结构倾向，这可能部分解释了这些多肽 GalNAc 转移酶所表现出的底物特异性的差异。
The tandem repeat of the MUC1 protein core is a major site of O-glycosylation that is catalyzed by several polypeptide GalNAc-transferases. To define structural features of the peptide substrates that contribute to acceptor substrate efficiency, solution structures of the 21-residue peptide AHGVTSAPDTRPAPGSTAPPA (AHG21) from the MUC1 protein core and four isoforms, glycosylated with alpha-N-acetylgalactosamine on corresponding Thr residues, AHG21 (T5), AHG21 (T10), AHG21 (T17), and AHG21 (T5,T17), were investigated by NMR spectroscopy and computational methods. NMR studies revealed that sugar attachment affected the conformational equilibrium of the peptide backbone near the glycosylated Thr residues. The clustering of the low-energy conformations for nonglycosylated and glycosylated counterparts within the VTSA, DTR, and GSTA fragments (including all sites of potential glycosylation catalyzed by GalNAc-T1, -T2, and -T4 transferases) showed that the glycosylated peptides display distinct structural propensities that may explain, in part, the differences in substrate specificities exhibited by these polypeptide GalNAc-transferases.