Identification of Cofragmented Combinatorial Peptide Isomers by Two-Dimensional Partial Covariance Mass Spectrometry.
Identification of Cofragmented Combinatorial Peptide Isomers by Two-Dimensional Partial Covariance Mass Spectrometry.
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DOI：
10.1021/jasms.3c00111
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发表时间：
2023-07-05
影响因子：
3.2
通讯作者：
Edelson-Averbukh, Marina
中科院分区：
文献类型：
--
作者：
Driver, Taran;Pipkorn, Ruediger;Averbukh, Vitali;Frasinski, Leszek J. J.;Marangos, Jon P. P.;Edelson-Averbukh, Marina
组合翻译后修饰（PTM），如那些形成所谓的“组蛋白密码”，已被链接到细胞分化，胚胎发育，细胞重编程，衰老，癌症，神经退行性疾病等，然而，一个可靠的质谱分析的组合异构体代表了相当大的挑战。困难源于信息的不完整性，可以产生的标准MS来区分共片段异构体序列在其天然存在的混合物的基础上的片段质荷比和相对丰度的信息。在这里，我们表明，片段-片段的相关性揭示了二维偏协方差质谱（2D-PC-MS）允许一个解决组合PTM难题，不能解决的标准MS作为一个原则问题。我们介绍了2D-PC-MS标记离子相关方法，并通过实验证明它可以提供缺失的信息，从而能够识别共片段组合修饰的异构体。我们的计算机模拟研究表明，标记离子相关性可以用来明确地确定5倍以上的cofractillated组合乙酰化胰蛋白酶肽和3倍以上的组合修饰的Glu-C肽的人组蛋白比可能使用标准MS方法。
Combinatorial post-translational modifications (PTMs), such as those forming the so-called “histone code”, have been linked to cell differentiation, embryonic development, cellular reprogramming, aging, cancers, neurodegenerative disorders, etc. Nevertheless, a reliable mass spectral analysis of the combinatorial isomers represents a considerable challenge. The difficulty stems from the incompleteness of information that could be generated by the standard MS to differentiate cofragmented isomeric sequences in their naturally occurring mixtures based on the fragment mass-to-charge ratio and relative abundance information only. Here we show that fragment–fragment correlations revealed by two-dimensional partial covariance mass spectrometry (2D-PC-MS) allow one to solve the combinatorial PTM puzzles that cannot be tackled by the standard MS as a matter of principle. We introduce 2D-PC-MS marker ion correlation approach and demonstrate experimentally that it can provide the missing information enabling identification of cofragmentated combinatorially modified isomers. Our in silico study shows that the marker ion correlations can be used to unambiguously identify 5 times more cofragmented combinatorially acetylated tryptic peptides and 3 times more combinatorially modified Glu-C peptides of human histones than is possible using standard MS methods.
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影响因子：
4
作者：
Doll, Sophia;Burlingame, Alma L.
通讯作者：
Burlingame, Alma L.
影响因子：
7
作者：
Sidoli, Simone;Kori, Yekaterina;Garcia, Benjamin A.
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Garcia, Benjamin A.
DOI：
10.1073/pnas.0710515105
发表时间：
2008-03-18
影响因子：
11.1
作者：
Phanstiel, Doug;Brumbaugh, Justin;Coon, Joshua J.
通讯作者：
Coon, Joshua J.
影响因子：
3.4
作者：
Britton LM;Gonzales-Cope M;Zee BM;Garcia BA
通讯作者：
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影响因子：
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作者：
Krautkramer, Kimberly A.;Reiter, Lukas;Dowell, James A.
通讯作者：
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