Proteins and Proteoforms: New Separation Challenges.

Proteins and Proteoforms: New Separation Challenges.
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DOI:
10.1021/acs.analchem.7b05007
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发表时间:
2018-01-02
影响因子:
7.4
通讯作者:
Kim J
Kim J
中科院分区:
化学1区
文献类型:
--
作者:
Regnier FE;Kim J

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古希腊人把生命归功于大自然母亲,抱怨她喜欢隐藏自己创造的东西。虽然我们不再把生命的奥秘归因于大自然,但生命系统的多个方面仍然让我们感到困惑。人类蛋白质组和蛋白质组家族的复杂性就是例子。直到最近,我们才相信人类大约20000个蛋白质编码基因中的每一个都产生一种蛋白质,假设这少量的蛋白质足以维持生命。错了!我们偏离了1-2个数量级。人类蛋白质组更可能由一百万种蛋白质组成。2-4接下来的问题是这些蛋白质是如何产生的以及它们的作用。质谱(MS)在蛋白质组学中有很大的帮助,但气相离子不能揭示体内生物合成和功能。分离蛋白质仍然是建立其三维结构和功能所必需的。下面的讨论是针对发现和鉴定以前未鉴定的蛋白质所涉及的分析和分离策略,需要关注下面发现的基因和组蛋白。作为细胞调控和诊断的一部分,监测已知蛋白质的结构和浓度的变化是蛋白质组学的一个同样重要的部分,但在这篇综述中没有提到。
The ancient Greeks attributed life to Mother Nature, complaining that she was fond of hiding the workings of her creations. Although we no longer attribute the mysteries of life to Mother Nature, multiple facets of living systems still evade us. The complexity of the human proteome and proteoform families are examples. Until recently we believed that each of the~ 20 000 protein-coding genes in humans produced a single protein, 1 assuming this small number of proteins was sufficient to sustain life. Wrong! We were off by 1–2 orders of magnitude. The human proteome is more likely to be made up of a million protein species. 2–4 Then there is the question of how these proteins arise and what they do. Mass spectrometry (MS) has been enormously helpful in proteomics, but gas phase ions do not reveal in vivo biosynthesis and function. Isolating proteins will still be necessary to establish their 3D structure and function.The discussion below is directed toward analytical and separation strategies involved in the discovery and identification of previously unidentified proteins, necessitating the focus on genes and histones found below. Monitoring changes in the structure and concentration of known proteins as part of cellular regulation and diagnostics is an equally important part of proteomics but not addressed in this review.
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