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© The Rockefeller University Press, 0021-9525/2002/11/538-a $5.00
The Journal of Cell Biology, Volume 159, Number 4, 538-a-539

Polyamino acids take amyloid form

Although lacking a specific side–chain pattern, polythreonine forms amyloid-like fibers. Dobson/EMBO

The folding of a polypeptide is a tug-of-war with bonds within the main chain fighting against interactions between the side chains, according to new results from Marcus Fändrich (IMB, Jena, Germany) and Christopher Dobson (University of Cambridge, Cambridge, UK). The winner determines whether a polypeptide forms a well-behaved globular structure or the dangerous amyloid fibrils that are associated with diseases such as Alzheimer's or Parkinson's.

Protein folding depends on specific side–chain interactions, but the new results show that amyloid formation does not. The authors examined polyamino acids (PAAs), peptide repeats of one amino acid that cannot fold into globular structures. Repeats of lysine, glutamine, and other amino acids were, however, able to form fibers with the distinctive cross-ß structure of amyloids. "Proteins are defined by the sequence of their side chains," says Fändrich. "PAAs don't have sequence patterns, but still give rise to amyloids. This means [that amyloid] structure isn't defined by the side chains and their interactions, but rather by the main chain." It may also explain why proline insertions, which alter the main chain, perturb amyloid formation.

Depending on the environment, some PAA side chains were more resistant to amyloid formation than others, however. Charged side chains resisted amyloid formation, probably because they are difficult to align within the densely packed ß sheets. Indeed, the most common repeat associated with amyloid diseases is glutamine, an uncharged amino acid.

But glutamine is not the only amyloid-forming side chain. Recently, alanine and leucine expansions were also noted in diseases or associated with nuclear fibers. Fändrich is not surprised. "People said it was the [glutamine] side chains—that they could interact by hydrogen bonds," he says. "Our data say polylysine and polythreonine work just as well. I imagine this is a more general phenomenon, and we are just realizing how important it is."

Reference:

Fändrich, M., et al. 2002. EMBO J. 21:5682–5690.[CrossRef][Medline]

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article Full Text (PDF, 631K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                            What's this?