PDB-wide identification of biological assemblies from conserved quaternary structure geometry
PDB-wide identification of biological assemblies from conserved quaternary structure geometry
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DOI：
10.1038/nmeth.4510
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发表时间：
2018-01-01
期刊：
影响因子：
48
通讯作者：
Levy, Emmanuel D.
中科院分区：
文献类型：
--
作者：
Dey, Sucharita;Ritchie, David W.;Levy, Emmanuel D.
蛋白质结构是理解生物分子机制和疾病的关键，但它们的解释受到其生物学相关四级结构（QS）的有限知识的阻碍。从晶体学数据推断QS信息的一个关键挑战是区分生物界面和偶然的晶体堆积接触。在这里，我们解决了这个问题，通过制定战略，调整和比较QS状态在同系物和数据存储库。跨同源物的QS保守性证明在预测生物相关性方面非常强，并且在两种方法中实施，QSalign和反QSalign，分别用于注释同源寡聚物和单体。在QSbio（http：//www.example.com）中实现了跨存储库的QS保存，其接近手动管理的准确性，并允许我们预测蛋白质数据库中的> 100，000个QS状态。www.QSbio.org基于这个高质量的数据集，我们分析了对结构保守的接口，这种分析揭示了一个惊人的可塑性，即进化遥远的接口保持相似的相互作用的几何形状，通过广泛不同的化学性质。
Protein structures are key to understanding biomolecular mechanisms and diseases, yet their interpretation is hampered by limited knowledge of their biologically relevant quaternary structure (QS). A critical challenge in inferring QS information from crystallographic data is distinguishing biological interfaces from fortuitous crystal-packing contacts. Here, we tackled this problem by developing strategies for aligning and comparing QS states across both homologs and data repositories. QS conservation across homologs proved remarkably strong at predicting biological relevance and is implemented in two methods, QSalign and anti-QSalign, for annotating homo-oligomers and monomers, respectively. QS conservation across repositories is implemented in QSbio (http://www.QSbio.org), which approaches the accuracy of manual curation and allowed us to predict >100,000 QS states across the Protein Data Bank. Based on this high-quality data set, we analyzed pairs of structurally conserved interfaces, and this analysis revealed a striking plasticity whereby evolutionary distant interfaces maintain similar interaction geometries through widely divergent chemical properties.