An amino acid code to define a protein's tertiary packing surface
An amino acid code to define a protein's tertiary packing surface
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DOI：
10.1002/prot.24966
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发表时间：
2016-02-01
影响因子：
2.9
通讯作者：
Tsai, Jerry
中科院分区：
文献类型：
--
作者：
Fraga, Keith J.;Joo, Hyun;Tsai, Jerry
蛋白质折叠问题的一个困难方面是描述定义蛋白质三级结构中堆积的非特定相互作用。为了更好地理解三级结构，本工作扩展了旋钮插座模型，将单个旋钮残基的相互作用分类为一组连续的插座，或由4个或更多残基组成的口袋。KnobSocket结构允许对口袋进行象征性的二维映射。口袋的二维映射提供了一种简单的方法来研究口袋形状的多样性，以了解蛋白质三级表面的几何形状。口袋几何形状的多样性可以组织成共享同一核心的口袋组，这表明口袋中的某些相互作用是包装的辅助作用。对口袋几何结构的进一步分析显示，在阿尔法螺旋中是右手的，在贝塔片中是左手的。袋子的氨基酸组成说明了非极性氨基酸在包装中的重要性以及位置的特异性。正如预期的那样，所有口袋形状都喜欢装上疏水旋钮；然而，旋钮对它们装入的口袋没有选择性。研究某些口袋形状的侧链旋转异构体偏好发现没有很强的相关性。这些发现允许基于旋钮和插座的简单词汇表来描述支持改进的蛋白质结构分析、设计和预测的蛋白质三级堆积。(C)2015年威利期刊公司。
One difficult aspect of the protein-folding problem is characterizing the nonspecific interactions that define packing in protein tertiary structure. To better understand tertiary structure, this work extends the knob-socket model by classifying the interactions of a single knob residue packed into a set of contiguous sockets, or a pocket made up of 4 or more residues. The knobsocket construct allows for a symbolic two-dimensional mapping of pockets. The two-dimensional mapping of pockets provides a simple method to investigate the variety of pocket shapes to understand the geometry of protein tertiary surfaces. The diversity of pocket geometries can be organized into groups of pockets that share a common core, which suggests that some interactions in pockets are ancillary to packing. Further analysis of pocket geometries displays a preferred configuration that is right-handed in alpha-helices and left-handed in beta-sheets. The amino acid composition of pockets illustrates the importance of nonpolar amino acids in packing as well as position specificity. As expected, all pocket shapes prefer to pack with hydrophobic knobs; however, knobs are not selective for the pockets they pack. Investigating side-chain rotamer preferences for certain pocket shapes uncovers no strong correlations. These findings allow a simple vocabulary based on knobs and sockets to describe protein tertiary packing that supports improved analysis, design, and prediction of protein structure. (C) 2015 Wiley Periodicals, Inc.