Researchers in the UK and Japan have identified core protein structural elements that may be important in amyloid fibril formation. These findings, reported in the May issue of Nature Structural Biology, now provide a structural framework for understanding the fibril formation process, and may ultimately aid in designing treatments for amyloid diseases, including Alzheimer’s disease, CJD, and dialysis-related amyloidosis..
The fibrils of Beta 2-microglobulin (Beta 2 m) are associated with amyloidosis in patients undergoing hemodialysis. To understand how functional protein molecules turn into fibrils, Sheena Radford and coworkers (University of Leeds) determined the most stable regions of the amyloid-forming intermediate of Beta 2 m. The regions roughly correspond to the core Beta-sheets in the functional Beta 2 m and have features remarkably similar to those seen in another amyloid disease-associated protein, transthyretin.
In an independent study, Yuji Goto and colleagues (Osaka University) and collaborators (the National Institute of Advanced Industrial Science and Technology, and Fukui University) examine the structure present at the other extreme of the fibril formation process ů that is, in the assembled Beta 2 m amyloid fibrils. Their results suggested that the functional protein structure is partially reconfigured during formation of the amyloid cross-Beta-sheet structure. Notably, the core structure in the fibril is very similar to that in the amyloid-forming intermediate. These results suggest that partially ordered b-sheets may play an important role in the formation of the cross-Beta-sheet structures that ultimately assemble into amyloid fibrils.
Sheena E. Radford
University of Leeds, UK
Tel: +44 1132 333 112
Osaka University, Japan
Tel: +81 6 6879 8614
Additional contact for comment on paper:
Jeffrey W. Kelly
Scripps Research Institute
La Jolla, USA
Tel: +1 858 784 9880
Published Online1 and
(C) Nature Structural Biology press release.
Message posted by: Trevor M. D'Souza
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