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首页> 外文期刊>Journal of Molecular Biology >Interdomain contact regions and angles between adjacent short consensus repeat domains.
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Interdomain contact regions and angles between adjacent short consensus repeat domains.

机译：域间接触区域和相邻的短共有重复序列域之间的角度。

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摘要

The short consensus repeat domain (SCR, complement control protein module, sushi-domain) is a structural unit found in multiple adjacent copies in more than 40 human proteins. Each bead-like domain is composed of approximately 60 residues and the adjacent domains are connected in a head-to-tail fashion with linkers that consist of two to 12 amino acid residues. Based on experimentally determined structures the neighbouring SCR domains interact with each other at the so-called hinge or interdomain contact region. The functions mediated by the SCR domains have been studied using mutagenesis but the possible effects of the mutations on the hinge regions and interdomain angles have not been analysed. In this study, the linker and three loops in conserved locations were found to be responsible for the interdomain contact regions of all the solved experimental structures. The interdomain contact regions were identified in sequences of 140 human SCR domain pairs, and distinct hydrophobic and charge features were found in different subsets of SCR proteins and functional domains. To compare the possible associations of the interdomain contact region characteristics to the interdomain orientations all the experimentally solved SCR structures were subjected to a uniform calculation of tilt, twist, and skew angles that define the interdomain orientation. The twist and skew angles were found to have a linear correlation and the spatial location of one loop of the N-terminal domain (N#1) was found to have an effect on the skew angle. Thus, we describe location of the interdomain contact regions in primary structures of SCR domains and report that the orientation of adjacent SCR domains is not random and depends partially on the interdomain contact regions. On the basis of these results, mutations within the interdomain contact regions and subsequent loss-of-function effects caused by changes in the interdomain orientation can be avoided in mutagenesis studies.
机译：短共有重复序列结构域（SCR，补体控制蛋白模块，sushi结构域）是在40多种人类蛋白的多个相邻拷贝中发现的结构单元。每个珠状结构域由大约60个残基组成，并且相邻的结构域以头到尾的方式与由2至12个氨基酸残基组成的接头连接。基于实验确定的结构，相邻的SCR域在所谓的铰链或域间接触区域相互相互作用。已经通过诱变研究了由SCR结构域介导的功能，但尚未分析突变对铰链区和结构域间角度的可能影响。在这项研究中，在保守位置的连接子和三个环被发现负责所有已解析实验结构的域间接触区域。在140个人SCR域对的序列中确定了域间接触区域，并在SCR蛋白和功能域的不同子集中发现了不同的疏水和电荷特征。为了将畴间接触区域特性与畴间取向的可能关联进行比较，对所有通过实验求解的SCR结构进行了定义畴间取向的倾斜角，扭曲角和偏斜角的均匀计算。发现扭曲角和倾斜角具有线性相关性，并且发现N末端域（N＃1）的一个环的空间位置对倾斜角有影响。因此，我们描述了域间接触区域在SCR域的主要结构中的位置，并报告了相邻SCR域的方向不是随机的，并且部分取决于域间接触区域。基于这些结果，在诱变研究中可以避免域间接触区域内的突变和随后因域间取向改变而引起的功能丧失效应。

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