Large-scale analysis of intrinsic disorder flavors and associated functions in the protein sequence universe

Large-scale analysis of intrinsic disorder flavors and associated functions in the protein sequence universe
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DOI:
10.1002/pro.3041
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发表时间:
2016-12-01
期刊:
影响因子:
8
通讯作者:
Tosatto, Silvio C. E.
Tosatto, Silvio C. E.
中科院分区:
生物学3区
文献类型:
--
作者:
Necci, Marco;Piovesan, Damiano;Tosatto, Silvio C. E.

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在过去的十年中,蛋白质中的内在紊乱(ID)已经被广泛描述;蛋白质中ID的大规模分类大多缺失。在这里,我们提供了一个广泛的分析ID在蛋白质宇宙的UniProt数据库中来自基于序列的预测在SDDB。几乎一半的序列含有至少五个残基的ID区域。约9%的蛋白质具有超过20个残基的长ID区域,其在真核生物中更丰富,并且最常见地覆盖小于20%的序列。约67,000(超过8000万)蛋白质的一小部分是完全无序的,主要存在于病毒中。大多数蛋白质只有一个ID,短ID沿序列沿着均匀分布,而长ID在中心过量。Das和Pappu的带电残基组合物被用于通过结构倾向和相应的功能富集对ID蛋白进行分类。Swedish Coils似乎主要用作原核生物和真核生物的结构成分和生物合成。在细菌中,它们被限制在类核中,在病毒中提供DNA结合功能。卷曲和发夹结构似乎专门参与核糖体结合和甲基化活动。小球和蝌蚪在真核生物中结合抗原,但在细菌中参与杀死其他生物和细胞溶解。细菌利用未定义的类来结合有毒物质,并介导病毒中生物体之间和内部的运输和运动。完全无序的蛋白质行为相似,但富含甘氨酸残基和细胞外结构。
Intrinsic disorder (ID) in proteins has been extensively described for the last decade; a large-scale classification of ID in proteins is mostly missing. Here, we provide an extensive analysis of ID in the protein universe on the UniProt database derived from sequence-based predictions in MobiDB. Almost half the sequences contain an ID region of at least five residues. About 9% of proteins have a long ID region of over 20 residues which are more abundant in Eukaryotic organisms and most frequently cover less than 20% of the sequence. A small subset of about 67,000 (out of over 80 million) proteins is fully disordered and mostly found in Viruses. Most proteins have only one ID, with short ID evenly distributed along the sequence and long ID overrepresented in the center. The charged residue composition of Das and Pappu was used to classify ID proteins by structural propensities and corresponding functional enrichment. Swollen Coils seem to be used mainly as structural components and in biosynthesis in both Prokaryotes and Eukaryotes. In Bacteria, they are confined in the nucleoid and in Viruses provide DNA binding function. Coils & Hairpins seem to be specialized in ribosome binding and methylation activities. Globules & Tadpoles bind antigens in Eukaryotes but are involved in killing other organisms and cytolysis in Bacteria. The Undefined class is used by Bacteria to bind toxic substances and mediate transport and movement between and within organisms in Viruses. Fully disordered proteins behave similarly, but are enriched for glycine residues and extracellular structures.