The images reveal that the filaments form a short zipper that is closed and stuck. To get a more realistic picture of what the fibrils look like, however, one should picture a towering stack of zippers, each of which is tightly bonded to the one below.
The first atomic details of the interconnected protein segments were reported in the June 9, 2005, issue of Nature.
In each disease, a different protein transforms into the misfolded threads known as amyloid fibrils. Scientists believe that the various proteins share a common underlying feature that explains how they assemble into the persistent fibrils that can accumulate in the brain and other tissues.
"To do something about these diseases, you have be able to see the parts at the atomic level," said senior author David Eisenberg, a Howard Hughes Medical Institute (HHMI) investigator at the University of California, Los Angeles. "Only then can you design an intervention."
The common trait of these different proteins was discovered more than thirty years ago. But even the most advanced technologies have been unable to capture anything more than a fuzzy image.
"We call it the spine of the amyloid," said Eisenberg, who is also director of the UCLA-Department of Energy Institute of Genomics and Proteomics. "A little bit of each protein forms the spine, and the rest of the protein is hanging out in globular domains that decorate the spine and give the fibril its thickness and bumpiness. Once these amyloid fibrils form in tissues or cells, they are very hard to get rid of."
Now, he and his colleagues report the first detailed look at one protein's version of the shared core feature.
Contact: Jim Keeley
Howard Hughes Medical Institute