Published online 7 April 2010 | Nature 464, 828-829 (2010) | doi:10.1038/464828a
News Feature
Protein folding: The dark side of proteins
Almost every human protein has segments that can form amyloids, the sticky aggregates known for their role in disease. Yet cells have evolved some elaborate defences, finds Jim Schnabel.
Jim Schnabel
Of all the ways that proteins can go bad, becoming an amyloid is surely one of the worst. In this state, sticky elements within proteins emerge and seed the growth of sometimes deadly fibrils. Amyloids riddle the brain in Alzheimer's disease and Creutzfeldt–Jakob disease. But until recently it has seemed that this corrupt state could threaten only a tiny fraction of proteins.
Research is now hinting at a more unsettling picture. In work reported in February, a team led by David Eisenberg at the University of California, Los Angeles, sifted through tens of thousands of proteins looking for segments with the peculiar stickiness needed to form amyloid1. They found, says Eisenberg, that "effectively all complex proteins have these short segments that, if exposed and flexible enough, are capable of triggering amyloid formation".
Protein segments with a 'steric zipper' structure mesh tightly to form the spine of amyloid fibrils.
M. R. Sawaya
Not all proteins form amyloids, however. The 'amylome', as Eisenberg calls it, is restricted because most proteins hide these sticky segments out of harm's way or otherwise keep their stickiness under control. His results and other work suggest that evolution treats amyloids as a fundamental threat. Amyloids have been found in some of the most common age-related diseases, and there is evidence that ageing itself makes some amyloid accumulation inevitable. It now seems as though the human body is perched precariously above an amyloidal abyss.
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