Biologists have developed a groundbreaking protein sequencing technique that involves pulling proteins through nanopores, paving the way for a deeper understanding of the human proteome.
Unlocking the Proteomic Puzzle
On the other hand, while the human genome has been mapped very well, our proteoforms have largely gone unexplored. The reason is that proteins are inherently three-dimensional.
But now a chemical biologist at the University of Washington, working with colleagues from Oxford Nanopore Technologies, has come up with an entirely new concept in protein sequencing. The researchers have added a dimension to the exploration of human proteome by pulling proteins through nanopores and unfolded them, probing the structural variations in these proteomic markers using an electric field.
Nanopore Sequencing Break Through
What makes this novel protein sequencing approach successful is the design of nanopores—little channels in a lipid membrane. At the other end of the protein, negatively charged sequences are now added to induce unfolding. The protein is then fed through the nanopore by an electric current, stretching it to its full length.
To keep the protein from being pulled through, and turned into spaghetti, they also included a — guess what? — stopper that straightens out the bar of protein even more as it passes through. You can imagine a protein moving (somewhat) slowly through the nanopore, carrying an electric charge that sends a signal down just past the stopper — this allows them to track changes in amplitude and map out the sequence of the protein.
This new technology, which draws from other ideas like the work of Hagan Bayley’s lab showing that nanopores could be used to pull individual ions through a liquid conduit, represents major progress in protein sequencing.
Conclusion
The development of the process by which proteins can be sequenced using a nanopore is a ground-breaking step for proteomics. By enabling the sequencing of the proteins encoded by a human genome, researchers can now study in greater detail how dozens of different protein structures work together to control human health and disease. The method is still in the early stages of development, but it offers a potential way for more medical discoveries and greater advances in personalized medicine.
