Deciphering structural elements of mucin glycoprotein recognition.
Deciphering structural elements of mucin glycoprotein recognition.
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DOI：
10.1021/cb300076s
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发表时间：
2012-06-15
影响因子：
4
通讯作者：
Live, David
中科院分区：
文献类型：
--
作者：
Borgert, Andrew;Heimburg-Molinaro, Jamie;Song, Xuezheng;Lasanajak, Yi;Ju, Tongzhong;Liu, Mian;Thompson, Pamela;Ragupathi, Govind;Barany, George;Smith, David F.;Cummings, Richard D.;Live, David
粘蛋白糖蛋白呈现复杂的结构景观，其由其众多丝氨酸和苏氨酸糖基化位点提供的糖基化模式的多样性引起，通常成簇，并且在各自的聚糖中具有变化。为了探索这种糖缀合物的结构复杂性，我们使用NMR系统地分析了一簇位点内糖基化密度的构象效应。这允许通过使用糖肽微阵列分析这些和其他糖肽与抗体、凝集素和血清之间的相互作用来与分子识别相关联。观察到选择性抗体与离散构象元件的相互作用，反映了GalNAc残基的肽和处置方面。我们的研究结果有助于弥合这些分子的构象特性和分子识别之间的差距，其生理作用的影响。天然粘蛋白基序的特征影响其相对免疫原性，并在抗体结合位点中准确编码，在分离的糖肽中保留了构象完整性，如抗体与阵列组分的结合谱所反映的。
Mucin glycoproteins present a complex structural landscape arising from the multiplicity of glycosylation patterns afforded by their numerous serine and threonine glycosylation sites, often in clusters, and with variations in respective glycans. To explore the structural complexities in such glycoconjugates we used NMR to systematically analyze the conformational effects of glycosylation density within a cluster of sites. This allows correlation with molecular recognition through analysis of interactions between these and other glycopeptides, with antibodies, lectins, and sera, using a glycopeptide microarray. Selective antibody interactions with discrete conformational elements, reflecting aspects of the peptide and disposition of GalNAc residues are observed. Our results help bridge the gap between conformational properties and molecular recognition of these molecules, with implications for their physiological roles. Features of the native mucin motifs impact their relative immunogenicity and are accurately encoded in the antibody binding site, with the conformational integrity being preserved in isolated glycopeptides, as reflected in the antibody binding profile to array components.
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DOI：
10.1073/pnas.0407902101
发表时间：
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影响因子：
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影响因子：
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影响因子：
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