Determination of the site-specific oligosaccharide distribution of the O-glycans attached to the porcine submaxillary mucin tandem repeat -: Further evidence for the modulation of O-glycan side chain structures by peptide sequence
Determination of the site-specific oligosaccharide distribution of the O-glycans attached to the porcine submaxillary mucin tandem repeat -: Further evidence for the modulation of O-glycan side chain structures by peptide sequence
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DOI：
10.1074/jbc.m111690200
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发表时间：
2002-03-08
影响因子：
4.8
通讯作者：
Zhang, JX
中科院分区：
文献类型：
--
作者：
Gerken, TA;Gilmore, M;Zhang, JX
目前对多肽序列和局部环境对o -链聚糖结构的调节程度知之甚少。在此基础上，研究人员确定了a型阴性猪颌下腺粘蛋白序列重复结构域中31个o-糖基化丝氨酸/苏氨酸残基中的29个位点特异性单- (GalNAc-O-)、二- (β - gal -1,3- α -GalNAc-O-)和三糖（α - fuc1,2- o- gal -1,3- α -GalNAc-O-）的分布。从三个个体动物身上获得的糖基化模式与早期对池粘蛋白的不完全测定一致(Gerken, t.a., Owens, c.l., and Pasumarthy， M. (1997) J. Biol。化学。272年,9709 - 9719;Gerken， T. A., Owens， C. L.，和Pasumarthy， M.（1998）。化学，273,2658026588)，证实了多肽连接的GalNAc的添加及其被β -1,3- gal取代对局部肽序列敏感，并且在体内具有高度可重复性。目前的数据进一步支持了先前提出的羟基氨基酸残基密度（以及肽GalNAc的密度）与肽连接的GalNAc被-1,3- gal取代的程度呈负相关的建议。这种效应与丝氨酸链聚糖高度相关，而与丝氨酸链聚糖无关。在体内多肽GalNAc糖基化模式中也观察到类似的相关性。相比之下，在β - gal上添加α -1,2- fuc与羟氨基酸密度没有明显的相关性，尽管可以观察到Ser-linked聚糖的聚焦化程度明显高于thrr -linked聚糖。上述效应可能代表了空间和构象因素的作用，以改变糖基转移酶对底物的相对可及性和活性。这些结果表明，猪颌下腺核心β 3-半乳糖转移酶和α 2-聚焦转移酶具有独特的肽/糖肽敏感性，可能为o链侧链结构的调节提供了机制。
Little is known of the degree that polypeptide sequence and the local environment modulate the structures of O-linked glycans. Toward this understanding, the site-specific mono- (GalNAc-O-), di- (beta-Gal-1,3-alpha-GalNAc-O-), and trisaccharide (alpha-Fuc-1,2-O-Gal-1,3-alpha-GalNAc-O-) distributions have been determined for 29 of the 31 O-glycosylated Ser/Thr residues in the tandem repeat domains of blood group A-negative porcine submaxillary gland mucin. The glycosylation patterns obtained from three individual animals are in agreement with earlier incomplete determinations on a pooled mucin (Gerken, T. A., Owens, C. L., and Pasumarthy, M. (1997) J. Biol. Chem. 272,9709-9719; Gerken, T. A., Owens, C. L., and Pasumarthy, M. (1998) J. Biol. Chem. 273, 2658026588), confirming that the addition of the peptide-linked GalNAc and its substitution by beta-1,3-Gal are sensitive to local peptide sequence in a highly reproducible manner in vivo. The present data further support earlier suggestions of an inverse correlation of the density of hydroxyamino acid residues (and by inference the density of peptide GalNAc) with the extent of substitution of the peptide-linked GalNAc by beta-1,3-Gal. This effect is highly correlated for Ser-linked glycans but not for Thr-linked glycans. A similar correlation is observed with respect to the in vivo peptide GalNAc glycosylation pattern. In contrast, the addition of alpha-1,2-Fuc to beta-Gal shows no apparent correlation with hydroxyamino acid density, although a marked elevation in the fucosylation of Ser-linked glycans compared with Thr-linked glycans is observed. The above effects may represent both steric and conformational factors acting to alter the relative accessibility and activity of the glycosyltransferases toward substrate. These results demonstrate that the porcine submaxillary gland core beta3-galactosyltransferase and alpha2-fucosyltransferase exhibit unique peptide/glycopeptide sensitivities that may provide mechanisms for the modulation of O-linked side chain structures.