Using new techniques to detect and sequence individual proteins

Identifying proteins in a sample is a crucial step in diagnosing many diseases and studying biological processes. However, sequencing proteins is a challenging task because protein structure is vastly more complex and varied than DNA. In addition, many proteins occur in small quantities, so traditional sequencing methods require large sample sizes and complex purification methods, and they still may not detect proteins only present in trace amounts.

Brady and Meyer reviewed a collection of techniques for single-molecule protein sequencing (SMPS), which have the potential to sequence and identify proteins in small samples or at low concentrations.

“A number of different approaches to single-molecule protein sequencing are currently being developed, each with their own unique opportunities and advantages,” said author Anne Meyer. “We provide an in-depth analysis of the technical details of each of these major new approaches, along with outlook on how each one may be able to develop into a successful technological platform.”

The authors examine five different emerging technologies: nanopore mass spectrometry, fluorescence-based methodologies, recognition tunneling, and synthetic and biological nanopores. Their goal is to introduce more people to the utility of SMPS and enable collaboration between disciplines to improve the technology.

“We hope our review will draw attention to these exciting and much needed technologies,” said author Morgan Brady. “SMPS is truly a multi-disciplinary field requiring input from a global scientific community. With further optimization, SMPS technologies would permit extraordinary power to clinicians and researchers for a variety of purposes.”

Source: “Cataloguing the proteome: Current developments in single-molecule protein sequencing,” by Morgan M. Brady and Anne S. Meyer, Biophysics Reviews (2022). The article can be accessed at https://doi.org/10.1063/5.0065509 .