β-Propeller blades as ancestral peptides in protein evolution.

β-Propeller blades as ancestral peptides in protein evolution.
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DOI:
10.1371/journal.pone.0077074
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Lupas AN
Lupas AN
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kopec KO;Lupas AN

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β-螺旋桨折叠的蛋白质本质上是普遍存在的,并广泛用作结构支架,用于配体结合和酶促活性。 - 孔形。 β-螺旋桨通过扩增和祖先叶片的多样化而产生β-螺旋桨,鉴于β-螺旋桨的结构多功能性以及第一个折叠的蛋白质是从更简单的辣椒中演变而来的同样,我们使用序列比较,将其他四个折叠的蛋白质视为β-螺旋桨的潜在同源物:肌醇酶的腔内域1 (IRE1-LD),II型β-晶体,β-Pinwheels和WW结构域,因为随着进化距离的增加和序列的减小,序列比较的统计显着性变得更加困难通过一种新方法完成了我们的分析,该方法根据序列和结构相似性评估可能的同源性。 IRE1-LD和II型β-优势与β-螺旋桨的关系,以及用于β-细胞轮和WW结构域的类似的关系。 II型β-PRISM是由单个叶片的扩增和分化,也可能是PQQ类型。刀片大小的碎片,代表了古老的肽世界的残留物。
Proteins of the β-propeller fold are ubiquitous in nature and widely used as structural scaffolds for ligand binding and enzymatic activity. This fold comprises between four and twelve four-stranded β-meanders, the so called blades that are arranged circularly around a central funnel-shaped pore. Despite the large size range of β-propellers, their blades frequently show sequence similarity indicative of a common ancestry and it has been proposed that the majority of β-propellers arose divergently by amplification and diversification of an ancestral blade. Given the structural versatility of β-propellers and the hypothesis that the first folded proteins evolved from a simpler set of peptides, we investigated whether this blade may have given rise to other folds as well. Using sequence comparisons, we identified proteins of four other folds as potential homologs of β-propellers: the luminal domain of inositol-requiring enzyme 1 (IRE1-LD), type II β-prisms, β-pinwheels, and WW domains. Because, with increasing evolutionary distance and decreasing sequence length, the statistical significance of sequence comparisons becomes progressively harder to distinguish from the background of convergent similarities, we complemented our analyses with a new method that evaluates possible homology based on the correlation between sequence and structure similarity. Our results indicate a homologous relationship of IRE1-LD and type II β-prisms with β-propellers, and an analogous one for β-pinwheels and WW domains. Whereas IRE1-LD most likely originated by fold-changing mutations from a fully formed PQQ motif β-propeller, type II β-prisms originated by amplification and differentiation of a single blade, possibly also of the PQQ type. We conclude that both β-propellers and type II β-prisms arose by independent amplification of a blade-sized fragment, which represents a remnant of an ancient peptide world.
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