This week in class we learned about alpha helices and beta sheets in protein structures. It’s thought that prion proteins become infectious when some of their alpha helices are converted into beta forms. I did a little research to find more details on the structure of the normal and infectious structures of the prion protein, and found something interesting: Not only is the conversion mechanism between the two forms unknown, but the structure of the infectious protein itself is unknown as well.
There have been recent, ongoing efforts to determine the structure of this protein (PrPSc), so I tried to find information that would be up-to-date. A paper from February, 2014 gave a good review of multiple attempts at modeling PrPSc, including both the methods of determining the model and the proposed structures. The methods of determining the structure included techniques such as Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), and X-ray crystallography.
One interesting fact that I learned is that old analyses of PrPSc thought that alpha-helices made up some portion of the protein because of FTIR data. There was a specific peak on the spectra that had been attributed to alpha helices, but it turned out later on that this peak showed up even when no alpha helices were present. Therefore, we cannot be sure whether PrPSc contains any alpha helices or not.
Another interesting fact that I learned is that many scientists who model PrPSc seem to think that there might be a beta helix present in the molecule rather than a beta sheet like the ones we learned about in class. A beta helix is a spiral of multiple beta strands (the straight, individual strands of amino acids that make up beta sheets). This structure would be stabilized by the same kinds of hydrogen bonds that we learned about. A beta helix might look something like the image below, where each arrow is an individual beta strand:
Overall, it’s cool to think about all the secondary structures that might be present in proteins, and how scientists try to go about determining which of those structures a molecule has.
It’s interesting that the current technology does not let researchers accurately identify what an alpha helix looks like. From what I understood, they got false positive readings on what an alpha helix was. Also interesting that alpha helixes + beta spirals can be combined to make the shape in the picture above. If something that complex is a secondary structure, I wonder what a tertiary structure looks like (from my 9th grade bio, I believe there is such thing).