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J Am Chem Soc. 2018 Sep 12;140(36):11495-11501. doi: 10.1021/jacs.8b07461. Epub 2018 Aug 29.

Measuring Ligand Binding Kinetics to Membrane Proteins Using Virion Nano-oscillators.

Ma G1, Syu GD2,3,4, Shan X1,5, Henson B2, Wang S1, Desai PJ2, Zhu H3,4, Tao N1,5.

Author information

1
Biodesign Center for Bioelectronics and Biosensors , Arizona State University , Tempe , Arizona 85287 , United States.
2
Viral Oncology Program , The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins , Baltimore , Maryland 21231 , United States.
3
Department of Pharmacology and Molecular Sciences , Johns Hopkins School of Medicine , Baltimore , Maryland 21205 , United States.
4
Center for High-Throughput Biology , Johns Hopkins School of Medicine , Baltimore , Maryland 21205 , United States.
5
School of Electrical, Computer and Energy Engineering , Arizona State University , Tempe , Arizona 85287 , United States.

Abstract

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.

PMID:
30114365
PMCID:
PMC6211285
DOI:
10.1021/jacs.8b07461
[Indexed for MEDLINE]
Free PMC Article

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