Every living organism is made up of a plethora of three-dimensional protein complexes organized so efficiently that every characteristic of that protein is a vital part of life. Proteins are macromolecules made with strings of various combinations of 20 different amino acids, which can be coded from 4 different base pairs. These strings of data are then folded into different orientations at specific points to define the protein complex’s role in the body. A few examples of the roles of protein complexes are to code every living organism’s DNA, create muscle movements, transport organelles, regulate cell-to-cell communication, provide energy for basic bodily functions, and make up all the tissues in our bodies. Protein function and form are not only determined by the protein’s composition, but its orientation as well.
Why Study Proteins?
Small errors in proteins can cause various diseases, which is why the study of protein composition and orientation are vital to learning more about disorders and discovering treatments. Sickle cell anemia is a genetic disorder in which red blood cells are misshapen and cause blockages in organs. This disorder is caused by just one incorrect amino acid position in the primary structure of protein composition. Cystic Fibrosis is a disorder which creates a thick, sticky mucous in the lungs and digestive organs, often causing the victim to develop lung disease and die at around 35 years old. This disorder is caused by deletion of a single amino acid, which leads to a mis-folded protein. It is apparent that many major disorders are caused by errors in protein composition; therefore the study of proteins must be detailed and precise.
How to Study Proteins
There are two major methods by which to study protein complexes. Electron microscopy shows the researcher broad outlines of large protein complexes, however it doesn’t show the details of protein composition. X-ray crystallography shows the researcher small details of the protein, however it can only be applied to a small portion of the protein at a time. Therefore, the two methods are currently used in conjunction to determine how the detailed pieces fit together to create a protein complex. Both of these technologies require fixed tissue samples, therefore researchers are only able to capture a protein’s characteristics at a single point in time and not in a living tissue.
New Techniques to Understand Protein Complexes
Rockefeller University scientists Dr. Sanford Simon, Alexa Mattheyses, Claire Atkinson, and Martin Kampmann strove to develop a technique to measure how components of a large protein are arranged among surrounding proteins. The premise behind their goal was to be able to learn about the orientation of the nuclear pore complex and its functions to further study major protein-driven processes, such as DNA transcription. Dr. Simon’s team achieved their goal by creating a technique using polarized light to construe the orientation of a specific protein within a cluster. The team attached markers to specific genetic components of the complex to create fluorescent tags so that tissue samples don’t need to be fixed and can be studied in live tissue. After this, the team used a customized microscope to measure the wave orientation of their implanted fluorescent tags. This new combination of technology should be used hand-in-hand with electron microscopy and X-ray crystallography to minimize technology shortcomings and create a more detailed and accurate picture of protein complexes. Details of this technology and its studies, including data analysis, formulas, polarization of the nuclear envelope, and fluorescence images have been published by Dr. Simon’s team in Biophysical Journal.
This new technique opens many doors to the future of protein study. Moving forward, the team’s discovery will be utilized by many researchers to study live cell environments in which protein configurations change over-time based on different stimuli. The advantages of studying protein reactions in live tissue are countless and will be applied to many protein-caused disorder studies in the future.
Amy S. Patel is a reliability engineer at Genentech and blogs about biomedical engineering on AmyPatel.com. She graduated from UC Irvine with a degree in Biomedical Engineering. Follow her on twitter: @BiobloggerAmyP
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