Computational prediction of O-linked glycosylation sites that preferentially map on intrinsically disordered regions of extracellular proteins.

Computational prediction of O-linked glycosylation sites that preferentially map on intrinsically disordered regions of extracellular proteins.
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DOI:
10.3390/ijms11124991
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发表时间:
2010
影响因子:
5.6
通讯作者:
Nishikawa K
Nishikawa K
中科院分区:
生物学2区
文献类型:
--
作者:
Nishikawa I;Nakajima Y;Ito M;Fukuchi S;Homma K;Nishikawa K

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哺乳动物蛋白质的O-糖基化是重要的翻译后修饰之一。我们应用支持向量机预测丝氨酸或苏氨酸是否是糖基化的,以阐明O-糖基化机制。O-糖基化位点通常沿着该序列聚集,而其他位点则零星分布。因此,我们开发了两种类型的支持向量机分别用于预测聚集性和孤立性位置。我们发现,氨基酸组成对于预测聚集型是有效的,而特定位点算法对于分离型是有效的。对聚集型的预测准确率最高为74%,对分离型的预测准确率最高为79%。O-糖基化位点周围氨基酸的存在频率在两种类型中是不同的,即Pro、Val和Ala在相对于糖基化位点的每个特定位置存在的概率很高,尤其是分离的类型。对O-糖基化位点附近氨基酸序列的独立成分分析表明,所鉴定的氨基酸作为独立成分存在于特定的位置。O-糖基化位点优先位于胞外蛋白质的固有无序区:尤其是,超过90%的聚集性O-GalNAc糖基化位点位于固有无序区。这一特征可能是理解O-糖基化的非保守性及其在功能多样性和结构稳定性中的作用的关键。
O-glycosylation of mammalian proteins is one of the important posttranslational modifications. We applied a support vector machine (SVM) to predict whether Ser or Thr is glycosylated, in order to elucidate the O-glycosylation mechanism. O-glycosylated sites were often found clustered along the sequence, whereas other sites were located sporadically. Therefore, we developed two types of SVMs for predicting clustered and isolated sites separately. We found that the amino acid composition was effective for predicting the clustered type, whereas the site-specific algorithm was effective for the isolated type. The highest prediction accuracy for the clustered type was 74%, while that for the isolated type was 79%. The existence frequency of amino acids around the O-glycosylation sites was different in the two types: namely, Pro, Val and Ala had high existence probabilities at each specific position relative to a glycosylation site, especially for the isolated type. Independent component analyses for the amino acid sequences around O-glycosylation sites showed the position-specific existences of the identified amino acids as independent components. The O-glycosylation sites were preferentially located within intrinsically disordered regions of extracellular proteins: particularly, more than 90% of the clustered O-GalNAc glycosylation sites were observed in intrinsically disordered regions. This feature could be the key for understanding the non-conservation property of O-glycosylation, and its role in functional diversity and structural stability.
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