Department of Genome Sciences, University of Washington, Seattle, Washington 98105, United States.
J Proteome Res. 2021 Jan 1;20(1):1087-1095. doi: 10.1021/acs.jproteome.0c00495. Epub 2020 Dec 2.
XLinkDB is a fast-expanding public database now storing more than 100 000 distinct identified cross-linked protein residue pairs acquired by chemical cross-linking with mass spectrometry from samples of 12 species (, (2), 753-758). Mapping identified cross-links to protein structures, when available, provides valuable guidance on protein conformations detected in the cross-linked samples. As more and more structures become available in the Protein Data Bank (, (1), 235-242), we sought to leverage their utility for cross-link studies by automatically mapping identified cross-links to structures based on sequence homology of the cross-linked proteins with those within structures. This enables use of structures derived from organisms different from those of samples, including large multiprotein complexes and complexes in alternative states. We demonstrate utility of mapping to orthologous structures, highlighting a cross-link between two subunits of mouse mitochondrial Complex I that was mapped to 15 structures derived from five mammals, its distances there of 16.2 ± 0.4 Å indicating strong conservation of the protein interaction. We also show how multimeric structures enable reassessment of cross-links presumed to be intraprotein as potentially homodimeric interprotein in origin.
XLinkDB 是一个快速发展的公共数据库，现在存储了超过 100000 对通过化学交联和质谱从 12 个物种的样本中获得的独特鉴定的交联蛋白残基对（，（2），753-758）。将鉴定的交联映射到蛋白质结构上，如果有可用的结构，为交联样品中检测到的蛋白质构象提供了有价值的指导。随着越来越多的结构在蛋白质数据库（，（1），235-242）中可用，我们试图通过基于交联蛋白与结构内蛋白的序列同源性自动将鉴定的交联映射到结构上来利用它们在交联研究中的效用。这使得可以使用与样品来源不同的生物体的结构，包括大型多蛋白复合物和替代状态下的复合物。我们展示了映射到同源结构的效用，突出了在来自五个哺乳动物的 15 个结构中映射到小鼠线粒体复合物 I 的两个亚基之间的交联，其距离为 16.2±0.4Å，表明蛋白质相互作用的强烈保守性。我们还展示了多聚体结构如何能够重新评估被假定为蛋白质内的交联作为潜在同源二聚体蛋白间的交联。
