This diagram shows the human protein and amino acid codes in the background. The new FRET X technology can identify proteins using protein fingerprints. Chirlmin Joo Lab obtains these unique fingerprints by finding parts of the full-length amino acid code (C and K highlighted in blue letters).Credit: Delft University of Technology
In a study published in natural nanotechnologyscientists at Delft University of Technology have introduced a new technique for identifying proteins.
Proteins perform important functions within our cells and also play an important role in diseases such as cancer and disease. COVID-19 (new coronavirus infection) infection. Researchers identify proteins by reading fingerprints and comparing them to patterns in a database.
Using this new technology, researchers can individually identify complete, full-length proteins while preserving all the information. This will help elucidate the mechanisms behind various diseases and enable early diagnosis.
Unfinished IKEA project
“The study of proteins in cells has been a hot topic for decades, and great progress has been made, giving researchers a better idea of what types of proteins there are and what functions they perform. ” said Mike Filius at the outset. Author of the paper.
Currently, scientists use a method called mass spectrometry to identify proteins. The most common mass spectrometry approach is the “bottom-up” approach, in which full-length proteins are cut into smaller fragments called peptides, which are then measured in a mass spectrometer.
Based on the data from these small pieces, a computer reconstructs the protein.
Filius: “It's a bit like a typical IKEA project, where you're always left with spare parts that you don't really know how to install. But in the case of Protein, these spare parts include It could actually contain something very valuable,” such as whether the protein has harmful structures that cause disease. ”
protein fingerprint
“You don't need to know all the proteins to identify them. amino acid; component of all proteins. Instead, we try to get enough information so that we can use the database as a reference to identify the protein, similar to how police identify a suspect from a fingerprint,” explains Filius. .
“In previous studies, we have shown that every protein has a unique fingerprint, just like its human analogue. To generate a unique fingerprint that can identify a protein, we need to “We realized that we only needed to know the positions of some of all the amino acids in a protein,” added Raman van Wee, a PhD candidate who worked on the research.
finding protein in a haystack
“These amino acids glow under the microscope and can be detected through molecules attached to small pieces of amino acids. DNA binds very specifically to certain amino acids acid” explains Van Wie.
In this way, the team can quickly determine the position of amino acids with great precision.
“The sensitivity of this new technology, called FRET ” Filius said. Say.
This is important because it allows us to measure patient samples in case of illness.
“Our paper shows that we can detect small amounts of proteins that are characteristic of Parkinson's disease and COVID-19,” Filius continued. “While other approaches have been investigated to identify proteins, our approach focuses on identifying complete individual proteins in complex mixtures.” You can also look for it,” Van Wie added.
For early diagnosis of diseases
Although promising, this research still requires significant development, which Chirlmin Joo Lab looks forward to working on. The research group spoke with several stakeholders in clinical laboratories and the biopharmaceutical industry and found that they were very excited about the breakthrough potential of this technology.
They are also working on launching a startup to develop FRET X into a highly sensitive protein detection platform. This platform can diagnose diseases at an early stage and improve the effectiveness of potential treatments.
“This breakthrough technology deciphers the protein code and opens up exciting possibilities for early disease detection,” said project supervisor Chirming Zhu. This was made possible by an amazing spirit of cooperation. “Everyone involved in our laboratory, as well as external colleagues including Martin Pabst’s laboratory from the Department of Biotechnology, Dick de Ridder (Wageningen University) and Geert-Jan Boons (Utrecht University), I would like to thank my collaborators,” Filius concluded.
Reference: “Full-length single molecule protein fingerprinting” Mike Filius, Raman van Wee, Carlos de Lannoy, Ilja Westerlaken, Zeshi Li, Sung Hyun Kim, Cecilia de Agrela Pinto, Yunfei Wu, Geert-Jan Boons, Martin Pabst, Dick・De Ridder and Charmin Zhu, February 13, 2024, natural nanotechnology.
DOI: 10.1038/s41565-023-01598-7
