Triggered Assembly of a DNA-Based Membrane Channel

被引:14
|
作者
Lanphere, Conor [1 ]
Ciccone, Jonah [1 ]
Dorey, Adam [1 ]
Hagleitner-Ertugrul, Nora [2 ]
Knyazev, Denis [2 ]
Haider, Shozeb [3 ]
Howorka, Stefan [1 ,2 ]
机构
[1] UCL, Inst Struct Mol Biol, Dept Chem, London WC1H 0AJ, England
[2] Johannes Kepler Univ Linz, Inst Appl Expt Biophys, A-4040 Linz, Austria
[3] UCL, Sch Pharm, Dept Pharmaceut & Biol Chem, London WC1N 1AX, England
基金
英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
SINGLE-MOLECULE KINETICS; DUPLEX FORMATION; HYBRIDIZATION KINETICS; CALCIUM INFLUX; ION CHANNELS; LIPOSOMES; DICHROISM; NANOPORES; VESICLES; ORIENTATION;
D O I
10.1021/jacs.1c06598
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Chemistry is in a powerful position to synthetically replicate biomolecular structures. Adding functional complexity is key to increase the biomimetics' value for science and technology yet is difficult to achieve with poorly controlled building materials. Here, we use defined DNA blocks to rationally design a triggerable synthetic nanopore that integrates multiple functions of biological membrane proteins. Soluble triggers bind via molecular recognition to the nanopore components changing their structure and membrane position, which controls the assembly into a defined channel for efficient transmembrane cargo transport. Using ensemble, single-molecule, and simulation analysis, our activatable pore provides insight into the kinetics and structural dynamics of DNA assembly at the membrane interface. The triggered channel advances functional DNA nanotechnology and synthetic biology and will guide the design of controlled nanodevices for sensing, cell biological research, and drug delivery.
引用
收藏
页码:4333 / 4344
页数:12
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