Protein Sequencing, One Molecule at a Time.
Protein Sequencing, One Molecule at a Time.
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DOI：
10.1146/annurev-biophys-102121-103615
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发表时间：
2022-05-09
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
--
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尽管在过去的十年里取得了巨大的进步，但蛋白质的表征方法总体上落后于核酸的方法，后者的特征是极高的灵敏度、动态范围和吞吐量。然而，直接在“核酸水平”表征蛋白质的能力将解决关键的生物学挑战，如更灵敏的医学诊断、更深入的蛋白质量化、大规模测量和发现替代蛋白质异构体和修饰，并将为单细胞蛋白质组学开辟新的途径。为了回应这一需求，人们一直在推动从根本上改进蛋白质测序技术，方法是从高通量核酸测序中获得灵感，特别是开发单分子蛋白质测序的实用方法。SMPS技术一般分为三类：降解测序(例如，质谱学或荧光测序)、运输测序(例如，纳米孔或量子隧道)和亲和测序(如基于DNA杂交的方法)。我们描述了这些不同的方法，从那些已经得到实验很好支持的方法，到在这个努力重构蛋白质组学的新生领域中仅仅是推测的方法。
Despite tremendous gains over the past decade, methods for characterizing proteins have generally lagged those for nucleic acids, which are characterized by extremely high sensitivity, dynamic range, and throughput. However, the ability to directly characterize proteins at “nucleic acid levels” would address critical biological challenges such as more sensitive medical diagnostics, deeper protein quantification, large-scale measurement and discovery of alternate protein isoforms and modifications, and would open new paths to single-cell proteomics. In response to this need, there has been a push to radically improve protein sequencing technologies by taking inspiration from high-throughput nucleic acid sequencing, with a particular focus on developing practical methods for single-molecule protein sequencing (SMPS). SMPS technologies fall generally into three categories: sequencing-by-degradation (such as e.g., mass spectrometry or fluorosequencing), sequencing-by-transit (e.g., nanopores or quantum tunneling), and sequencing-by-affinity (as in DNA hybridization-based approaches). We describe these diverse approaches, which range from those already experimentally well-supported to the merely speculative, in this nascent field striving to reformulate proteomics.
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影响因子：
38.3
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Brodbelt JS
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Brodbelt JS
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通讯作者：
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Borgo, Benjamin;Havranek, James J.
通讯作者：
Havranek, James J.