Tertiary alphabet for the observable protein structural universe
Tertiary alphabet for the observable protein structural universe
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DOI：
10.1073/pnas.1607178113
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发表时间：
2016-11-22
影响因子：
11.1
通讯作者：
Grigoryan, Gevorg
中科院分区：
文献类型：
--
作者：
Mackenzie, Craig O.;Zhou, Jianfu;Grigoryan, Gevorg
在这里，我们系统地将已知的蛋白质结构宇宙分解成其基本元素，我们称之为三级结构基序（TERM）。一个TERM是一个紧凑的骨架片段，它捕获给定残基周围的二级，三级和四级环境，包括一个或多个不相交的片段（平均三个）。我们寻求一套通用的TERMs，捕捉所有的结构在蛋白质数据库（PDB），发现显着的简并性。只有类似于600 TERM才足以在亚埃分辨率下描述50%的PDB。然而，也存在更罕见的几何形状，并且总体结构覆盖率随着TERMs的数量而几何地增长。我们继续表明，通用TERMs提供了一个有效的序列和结构之间的映射。我们表明，基于TERM-based的统计数据本身就足以概括接近天然的序列，无论是NMR或X-射线骨架。此外，从$TERM数据预测的序列变异性与进化变异密切相关.最后，基于PDB中TERM实例出现的序列签名，可以单独从序列预测蛋白质链中TERMs的位置。对于多片段基序，这种方法确定空间相邻的片段，是不连续的序列结构预测的一个主要瓶颈。尽管所有的TERMs都在不同的蛋白质中重复出现，但有些似乎专门用于某些功能，如界面形成，金属配位，甚至水结合。结构生物学从以前观察到的结构简并中受益匪浅。将已知的结构宇宙分解成一组有限的紧凑的TERMs，为更好地理解、设计和预测蛋白质结构提供了令人兴奋的机会。
Here, we systematically decompose the known protein structural universe into its basic elements, which we dub tertiary structural motifs (TERMs). A TERM is a compact backbone fragment that captures the secondary, tertiary, and quaternary environments around a given residue, comprising one or more disjoint segments (three on average). We seek the set of universal TERMs that capture all structure in the Protein Data Bank (PDB), finding remarkable degeneracy. Only similar to 600 TERMs are sufficient to describe 50% of the PDB at sub-Angstrom resolution. However, more rare geometries also exist, and the overall structural coverage grows logarithmically with the number of TERMs. We go on to show that universal TERMs provide an effective mapping between sequence and structure. We demonstrate that TERM-based statistics alone are sufficient to recapitulate close-to-native sequences given either NMR or X-ray backbones. Furthermore, sequence variability predicted from TERM data agrees closely with evolutionary variation. Finally, locations of TERMs in protein chains can be predicted from sequence alone based on sequence signatures emergent from TERM instances in the PDB. For multisegment motifs, this method identifies spatially adjacent fragments that are not contiguous in sequence-a major bottleneck in structure prediction. Although all TERMs recur in diverse proteins, some appear specialized for certain functions, such as interface formation, metal coordination, or even water binding. Structural biology has benefited greatly from previously observed degeneracies in structure. The decomposition of the known structural universe into a finite set of compact TERMs offers exciting opportunities toward better understanding, design, and prediction of protein structure.