Motivation

Polyproline II (PPII) is a common conformation, comparable to α-helix and β-sheet and is a candidate for being the most prevalent secondary structure. PPII, recently termed with a more generic name – κ-helix, adopts a left-handed structure with 3-fold rotational symmetry. Lately, a new type of binding mechanism – the helical lock and key model was introduced in SH3-domain complexes, where the interaction is characterized by a sliding helical pattern. However, whether this binding mechanism is unique only to SH3 domains is unreported.

Results

Here, we show that the helical binding pattern is a universal feature of the κ-helix conformation, present within all the major target families - SH3, WW, profilin, MHC-II, EVH1, and GYF domains. Based on a geometric analysis of 255 experimentally solved structures, we found that they are characterized by a distinctive rotational angle along the helical axis. Furthermore, we found that the range of helical pitch varies between different protein domains or peptide orientations and that the interaction is also represented by a rotational displacement mimicking helical motion. The discovery of rotational interactions as a mechanism, reveals a new dimension in the realm of protein-protein interactions, which introduces a new layer of information encoded by the helical conformation. Due to the extensive involvement of the conformation in functional interactions, we anticipate our model to expand the current molecular understanding of the relationship between protein structure and function.

Availability

We have implemented the proposed methods in an R package freely available at https://github.com/Grantlab/bio3d

Supplementary information

Supplementary dataSupplementary data are available at Bioinformatics online.

中文翻译：

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κ-螺旋和螺旋锁和钥匙模型：研究多脯氨酸II的关键方法。

动机

聚脯氨酸II（PPII）是一种常见的构象，与α-螺旋和β-片层相当，并且是最普遍的二级结构的候选者。PPII，最近被命名为κ螺旋，它采用左旋结构，具有3倍旋转对称性。最近，在SH3域复合物中引入了一种新型的绑定机制–螺旋锁和密钥模型，其中的相互作用以滑动螺旋模式为特征。但是，此绑定机制是否仅对SH3域是唯一的尚未报道。

结果

在这里，我们显示出螺旋结合模式是κ-螺旋构象的普遍特征，存在于所有主要靶标家族中-SH3，WW，profilin，MHC-II，EVH1和GYF域。根据对255个通过实验求解的结构的几何分析，我们发现它们的特征是沿螺旋轴的独特旋转角度。此外，我们发现螺旋间距的范围在不同的蛋白质结构域或肽方向之间变化，并且相互作用也由模仿螺旋运动的旋转位移表示。旋转相互作用作为一种机制的发现揭示了蛋白质-蛋白质相互作用领域的新维度，从而引入了由螺旋构象编码的新信息层。

可用性

我们已经在https://github.com/Grantlab/bio3d免费提供的R包中实现了建议的方法。

补充资料

补充数据补充数据可从Bioinformatics在线获得。