While we often think of diseases as caused by foreign bodies—bacteria or viruses—there are hundreds of diseases affecting humans that result from errors in cellular production of its proteins. A team of researchers led by the University of Massachusetts Amherst recently leveraged the power of cutting-edge technology, including an innovative technique called glycoproteomics, to unlock the carbohydrate-based code that governs how certain classes of proteins form themselves into the complex shapes necessary to keep us healthy.
The research, published in the journal Molecular Cell, explores members of a family of proteins called serpins, which are implicated in a number of diseases. The research is the first to investigate how the location and composition of carbohydrates attached to the serpins ensure that they fold correctly. Serious diseases—ranging from emphysema and cystic fibrosis to Alzheimer’s disease—can result when the cellular oversight of protein folding goes awry. Identifying the glyco-code responsible for high-fidelity folding and quality control could be a promising way for drug therapies to target many diseases.
The discovery of the carbohydrate-based chaperone system in the ER was due to the pioneering work that Daniel Hebert, professor of biochemistry and molecular biology at UMass Amherst and one of the paper’s senior authors, initiated as a postdoctoral fellow in the 1990s. “The tools we have now, including glycoproteomics and mass spectrometry at UMass Amherst’s Institute for Applied Life Sciences, are allowing us to answer questions that have remained open for over 25 years,” says Hebert. “The lead author of this new paper, Kevin Guay, is doing things I could only dream of when I first started.” Read more