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Biologists sequence proteins by pulling them through nanopores

A team of chemical biologists at the University of Washington, working with colleagues at Oxford Nanopore Technologies, has developed a protein sequencing process that involves pulling proteins through nanopores in a lipid membrane. Their paper is published in the journal Nature.

Prior research has shown that while the human genome has approximately 20,000 genes, there are more than 1 million associated protein structures known as proteoforms that allow for the great diversity between individual people. And while the genome has been sequenced, the proteoforms have not, due to their three-dimensional nature.

In this new study, the research team found a way to conduct such sequencing—by pulling the proteins through a nanopore and measuring their structural variations using an electric field.

The study builds on prior work by a host of other teams, such as an effort last year led by Hagan Bayley, one of the founders of Oxford Nanopore. That team found that nanopores could be used to select for particular ions in a liquid. In this new effort, the team found that nanopores in certain lipids can be used as a tool for sequencing proteins.

The process involves first unfolding the protein under study by adding negatively charged sequences to its tail and then using an electric current to pull on it, causing it to stretch out to its full length. The protein is then pulled through a naturally occurring nanopore in a lipid channel.