Unique Electrical Signature of Phosphate for Specific Single-Molecule Detection of Peptide Phosphorylation
Unique Electrical Signature of Phosphate for Specific Single-Molecule Detection of Peptide Phosphorylation
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DOI：
10.1021/jacs.2c05787
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发表时间：
2022-09-14
影响因子：
15
通讯作者：
Nishino，Tomoaki
中科院分区：
文献类型：
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作者：
Harashima，Takanori;Egami，Yoshiyuki;Nishino，Tomoaki
生物材料的单分子测量为细胞事件带来了新的见解。对于几乎所有这些事件，翻译后修饰(PTM)通过其化学修饰改变蛋白质的性质，构成了基本的调节机制。然而，适合于PTMS研究的单分子方法学非常有限。在这里，我们展示了基于电测量的多肽磷酸化的单分子检测，这是一种典型的PTM。我们发现，磷酸基团稳定地连接了金属电极之间的纳米间隙，并表现出高电导，这使得能够对多肽磷酸化进行特异性的单分子检测。目前的方法学为PTMS的单分子研究铺平了道路，如这里所示的蛋白质酶促修饰的单分子动力学。
Single-molecule measurements of biomaterials bring novel insights into cellular events. For almost all of these events, post-translational modifications (PTMs), which alter the properties of proteins through their chemical modifications, constitute essential regulatory mechanisms. However, suitable single-molecule methodology to study PTMs is very limited. Here we show single-molecule detection of peptide phosphorylation, an archetypal PTM, based on electrical measurements. We found that the phosphate group stably bridges a nanogap between metal electrodes and exhibited high electrical conductance, which enables specific single-molecule detection of peptide phosphorylation. The present methodology paves the way to single-molecule studies of PTMs, such as single-molecule kinetics for enzymatic modification of proteins as shown here.