Measuring Ligand Binding Kinetics to Membrane Proteins Using Virion Nano-oscillators.
Measuring Ligand Binding Kinetics to Membrane Proteins Using Virion Nano-oscillators.
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DOI：
10.1021/jacs.8b07461
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发表时间：
2018-09-12
影响因子：
15
通讯作者：
Tao N
中科院分区：
文献类型：
--
作者：
Ma G;Syu GD;Shan X;Henson B;Wang S;Desai PJ;Zhu H;Tao N
膜蛋白在细胞信号传导过程中起着至关重要的作用，是最受欢迎的药物靶点。研究细胞功能和开发药物的关键任务是测量配体与膜蛋白的结合动力学。然而，这一直是一个长期的挑战，因为人们必须在膜环境中进行测量，以维持膜蛋白的构象和功能。在这里，我们报告了一种使用自组装病毒粒子振荡器测量配体与膜蛋白结合动力学的新方法。利用人疱疹病毒的病毒粒子在其病毒包膜上显示人g蛋白偶联受体（gpcr）。然后，每个病毒粒子通过柔性聚合物附着在涂有金的玻璃表面上，形成一个振荡器，并在交变电场的驱动下振荡。通过亚纳米精度实时跟踪振荡振幅的变化，测量配体与gpcr的结合动力学。我们期望这种新的无标记检测技术可以很容易地应用于测量与任何类型膜蛋白结合的大小配体，从而有助于理解细胞功能和药物筛选。
Membrane proteins play vital roles in cellular signaling processes and serve as the most popular drug targets. A key task in studying cellular functions and developing drugs is to measure the binding kinetics of ligands with the membrane proteins. However, this has been a long-standing challenge because one must perform the measurement in a membrane environment to maintain the conformations and functions of the membrane proteins. Here, we report a new method to measure ligand binding kinetics to membrane proteins using self-assembled virion oscillators. Virions of human herpesvirus were used to display human G-protein-coupled receptors (GPCRs) on their viral envelopes. Each virion was then attached to a gold-coated glass surface via a flexible polymer to form an oscillator and driven into oscillation with an alternating electric field. By tracking changes in the oscillation amplitude in real-time with subnanometer precision, the binding kinetics between ligands and GPCRs was measured. We anticipate that this new label-free detection technology can be readily applied to measure small or large ligand binding to any type of membrane proteins and thus contribute to the understanding of cellular functions and screening of drugs.
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DOI：
10.1073/pnas.95.21.12271
发表时间：
1998-10-13
影响因子：
11.1
作者：
Höök, F;Rodahl, M;Brzezinski, P
通讯作者：
Brzezinski, P
影响因子：
2.9
作者：
Abdiche, Yasmina;Malashock, Dan;Pons, Jaurne
通讯作者：
Pons, Jaurne
DOI：
10.1038/nrd.2016.230
发表时间：
2017-01
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Santos R;Ursu O;Gaulton A;Bento AP;Donadi RS;Bologa CG;Karlsson A;Al-Lazikani B;Hersey A;Oprea TI;Overington JP
通讯作者：
Overington JP
单细胞中的原位药物受体结合动力学：抗肿瘤耐药性的定量无标记研究
影响因子：
4.6
作者：
Wang W;Yin L;Gonzalez-Malerva L;Wang S;Yu X;Eaton S;Zhang S;Chen HY;LaBaer J;Tao N
通讯作者：
Tao N
影响因子：
16.6
作者：
Klein Herenbrink C;Sykes DA;Donthamsetti P;Canals M;Coudrat T;Shonberg J;Scammells PJ;Capuano B;Sexton PM;Charlton SJ;Javitch JA;Christopoulos A;Lane JR
通讯作者：
Lane JR