What Makes Memory
Cytoplasmic Polyadenylation Element Binding Protein, or CPEB, is an amyloid-forming protein found to be associated with neuroplasticity. But how? See below.
i. sketching the story
Who is the protagonist, and what is their story? In this animation, I wanted to communicate the unlikely and little-known journey of the Cytoplasmic Polyadenlyation Element Binding Protein (CPEB). It has been known to form long, string-like amyloid fibers, much like the amyloid-forming proteins associated with Alzheimer's and mad cow disease. But CPEB does not damage the brain: interestingly enough, it has been associated with neuronal growth and remodeling. Below, you can see studies of the protein's structure in its unstable form, monomeric, trimeric, and tetrameric coiled-coil forms, and in amyloid form.
ii. the storyboard
During this phase, I sought to create a mysterious atmosphere when the viewer is taken through the tangles of neurons. Throughout the entire animation, the camera moves forward so that each step in the process moves smoothly to the next.
Because CPEB has large regions of intrinsic disorder, its structure is not stable. A key characteristic of amyloid-forming proteins, CPEB can exist in the cytoplasm as coiled-coil dimers, trimers, or tetramers. Mechanical force from actin and an increased concentration of CPEB can lead to amyloid fiber development. The amyloids activate mRNAs encoding for proteins needed for cellular growth.
iii. creating a 3d model
The primary challenge with modeling a representation of CPEB is that, because it has large regions of intrinsic disorder, its structure is largely unknown. Sites for RNA binding have been found (PDB:2MKH), but its structure and the conformational changes it undergoes are a mystery.
This section is under construction!
Thank you for your patience.
ii. the final animation
Chen, M., Zheng, W., & Wolynes, P. G. (2016). Energy landscapes of a mechanical prion and their implications for the molecular mechanism of long-term memory. Proceedings of the National Academy of Sciences, 113(18), 5006–5011. https://doi.org/10.1073/pnas.1602702113
Raveendra, B. L., Siemer, A. B., Puthanveettil, S. V., Hendrickson, W. A., Kandel, E. R., & McDermott, A. E. (2013). Characterization of prion-like conformational changes of the neuronal isoform of Aplysia CPEB. Nature Structural & Molecular Biology, 20(4), 495–501. https://doi. org/10.1038/nsmb.2503
Shorter, J., & Lindquist, S. (2005). Prions as adaptive conduits of memory and inheritance. Nature Reviews Genetics, 6(6), 435–450. https://doi. org/10.1038/nrg1616
Si, K., & Kandel, E. R. (2016). The Role of Functional Prion-Like Proteins in the Persistence of Memory. Cold Spring Harbor Perspectives in Biology, 8(4), a021774. https://doi.org/10.1101/cshperspect.a021774