Department of Molecular Reproduction, Development and Genetics, Indian Institute of Sciences, Bangalore, 560012, India.
School of Earth and Environmental Sciences, Central University of Himachal Pradesh, District-Kangra, Shahpur, Himachal Pradesh, 176206, India.
Sci Rep. 2020 Apr 8;10(1):6040. doi: 10.1038/s41598-020-61427-y.
Several post-translational protein modifications lie predominantly within regions of disorder: the biased localization has been proposed to expand the binding versatility of disordered regions. However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order. When compared with disordered stretches, ordered regions were not found to be enriched for asparagines, serines and threonines, residues that constitute the sequon signature for conjugation of N-glycans. We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures. When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures. N-glycosite neighborhoods also showed greater phylogenetic conservation among amniotes, compared with control ordered regions, which in turn were more conserved than disordered control regions. Our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches.
这种偏位定位被认为可以扩展无序区域的结合多样性。然而，在对 500 个人类 N-糖蛋白的代表性数据集进行研究后，我们观察到 N-连接糖基化或 N-糖基化位点主要存在于预测的有序区域。与无序延伸相比，有序区域中并未发现天冬酰胺、丝氨酸和苏氨酸富集，这些残基构成了 N-聚糖结合的序列特征。然后，我们基于氨基酸分布研究了无序和 N-糖基化位点之间相互排斥的基础：与没有任何 N-糖基化位点的对照有序残基延伸相比，N-糖基化位点周围的残基环境显示出大体积、疏水和促进无序的氨基酸耗尽，以及富含灵活和可及的残基，这些残基经常存在于卷曲结构中。与没有任何 N-糖基化位点的对照无序残基延伸相比，N-糖基化位点周围的残基环境中电荷、极性、疏水和灵活的残基耗尽，而富含芳香族、可及和促进有序的残基，这些残基倾向于成为卷曲和β结构的一部分。与对照有序区域相比，N-糖基化位点周围区域在羊膜动物中表现出更大的系统发育保守性，而对照有序区域的保守性又高于无序对照区域。我们的研究结果表明，独特的一级结构组成和对可进化性的不同倾向允许 N-糖基化位点周围区域和无序延伸的空间相互排斥。
