One of the ways in which proteins can ‘go wrong’ is something called protein misfolding. Proteins are made up of long, branching chains of amino acids, which tend to fold up into three-dimensional structures, rather like a piece of paper can be folded into an intricate origami structure.
This structure is key to how the protein behaves in the body. If a protein folds in the wrong way it can lead to diseases such as cancer, Alzheimer’s disease or Parkinson’s disease.
Scientists are therefore looking for ways to study how proteins fold and misfold, and how to spot potential problems.
Now, Yubin Zhou and his team at Texas A&M University have developed a method of following protein folding in real time in living cells. The protein can remain in its native environment – that is inside the cell – while it’s being studied, which makes the method much more applicable to real-life situations than studying the same protein in a test tube.
They have developed two types of marker – named “MoTags” – which they can attach to the protein at various points. The MoTags emit fluorescence, which can be detected using a simple fluorescence microscope – available as standard in many chemistry labs. The fluorescent tags make it possible for a scientist to observe the protein’s folding behaviour through a microscope.
Yubin Zhou and his team have already used the tags to study a dozen proteins with various 3D structures. By altering the proteins in small ways – such as changing their environment, or making tweaks to the amino acid chain – they can observe how these alterations affect the protein’s 3D structures. Crucially, they can watch these changes happen in real time, enabling them to gather a lot of data in a short period of time.
In the future this method should provide us with important information on the various factors that lead to protein misfolding diseases. Professor Zhou also anticipates that the method could be used to screen for drugs that could correct the misfolding of key proteins in disease.
This article is free to read in our open access, flagship journal Chemical Science: Guolin Ma et al., Chem. Sci., 2018, Accepted Manuscript, DOI: 10.1039/C8SC00839F