Closed since over 8 years ago
Intermediate PilotThe misfolding and aggregation of amyloid proteins underlies many diseases, including Alzheimer’s disease, Parkinson’s disease, and ALS. However, the process by which protein misfolding causes cell toxicity and death is still heavily debated. In this puzzle, players are provided with three copies of the Aβ peptide, which forms amyloid fibrils in the brains of those afflicted with Alzheimer’s disease. In addition to amyloid fibrils, Aβ is known to form small soluble clusters. There is some evidence that these small clusters are more toxic than the amyloid fibrils, but the structure of such Aβ clusters is still unknown. In this puzzle, players can explore the different possibilities for how these small clusters of Aβ might fold.
This is another puzzle in our Classroom Series. University of Denver students will be asked to read two articles alongside this Foldit puzzle. The first is a 2007 paper by Cheng et al., who present evidence that, for the Aβ protein, higher levels of soluble oligomers—not amyloid fibrils—are more strongly associated with brain dysfunction in mice. The second 2012 paper by Pieri et al. shows that, for α-synuclein and huntington proteins, the amyloid fibrils are indeed toxic to cells in vitro.
Usually the only 'multiple segments' proteins I see are the mirror-image ones…which usually crash on my client… But this seems to be folding nicely, only it's so complex for my tiny little brain that I'm sitting back and letting my GAB recipes do their magic!
