Sculpting conducting nanopore size and shape through de novo protein design

• 成果类型: Article
• 署名作者: Berhanu, Samuel; Majumder, Sagardip; Muentener, Thomas; Whitehouse, James; Berner, Carolin; Bera, Asim K.; Kang, Alex; Liang, Binyong; Khan, Nasir; Sankaran, Banumathi; Tamm, Lukas K.; Brockwell, David J.; Hiller, Sebastian; Radford, Sheena E.; Baker, David; Vorobieva, Anastassia A.
• 署名单位: University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Basel; University of Leeds; Vrije Universiteit Brussel; Flanders Institute for Biotechnology (VIB); University of Virginia; University of Virginia; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10769
• DOI: 10.1126/science.adn3796
• 发表日期: 2024-07-19
• 关键词: beta-barrel proteins; thermodynamic stability; principles; prediction

摘要

Transmembrane beta-barrels have considerable potential for a broad range of sensing applications. Current engineering approaches for nanopore sensors are limited to naturally occurring channels, which provide suboptimal starting points. By contrast, de novo protein design can in principle create an unlimited number of new nanopores with any desired properties. Here we describe a general approach to designing transmembrane beta-barrel pores with different diameters and pore geometries. Nuclear magnetic resonance and crystallographic characterization show that the designs are stably folded with structures resembling those of the design models. The designs have distinct conductances that correlate with their pore diameter, ranging from 110 picosiemens (similar to 0.5 nanometer pore diameter) to 430 picosiemens (similar to 1.1 nanometer pore diameter). Our approach opens the door to the custom design of transmembrane nanopores for sensing and sequencing applications.