The danger of misfolded proteins

Protein folding intermediates are cytotoxic, independent of cell damage caused by mature folded proteins.

Tudor Toma(t.toma@ic.ac.uk)
Apr 8, 2002

The function of a protein depends on the precise three-dimensional structure of its folded forms, but errors in the folding process occur and can have serious consequences. Two papers in April 4 Nature show that intermediates in protein folding can damage cells and be dangerous themselves, independent of toxicity shown by mature folded proteins.

Monica Bucciantini and colleagues from Universita degli Studi di Firenze, Italy, observed that polypeptide species formed early in the aggregation of PI-SH3 and HypF-N proteins are highly cytotoxic. These proteins are similar to the proteins involved in clinical amyloidoses but are not associated with the disease. In both cases, the cytotoxicity was found to depend on the supramolecular organization of the aggregates and is much more pronounced for the rapidly formed non-fibrillar aggregates than for the highly organized fibrillar structures (Nature 2002, 416:507-511).

In a second study, Dominic Walsh and colleagues from Harvard...

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