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An Atomic Look at a Toxic Amyloid Small Oligomer Print
Thursday, 06 September 2012 09:30

 

Amyloids are insoluble fibrous protein aggregates sharing specific structural traits. Amyloid diseases, including Alzheimer’s, Parkinson’s, and the prion conditions, are each associated with a particular protein in fibrillar form. These amyloid fibrils were long suspected to be the disease agents, but evidence now suggests that smaller, often transient and polymorphic oligomers (molecules containing a few monomers) are the toxic entities. Researchers from the University of California, Los Angeles, Howard Hughes Medical Institute, and the UCLA-DOE Institute for Genomics and Proteomics used ALS Beamline 8.2.1 to identify a segment of the amyloid-forming protein αB crystallin, which forms an oligomeric complex exhibiting properties of other amyloid oligomers: β-sheet–rich structure, cytotoxicity, and recognition by an oligomer-specific antibody. The x-ray–derived atomic structure of the oligomer reveals a cylindrical barrel formed from six antiparallel protein strands called a cylindrin. The cylindrin structure is compatible with a sequence segment from the β-amyloid protein of Alzheimer’s disease. Cylindrins offer models for other, still-elusive structures of amyloid oligomers.

 

Ribbon representation of the cylindrin crystal structure formed from six antiparallel protein strands. Pairs of strands form antiparallel dimers, which assemble around a threefold axis down the barrel axis (left). A dry interior cavity is formed by triplets of Val residues, shown as spheres, at the top and bottom (right).

 


 

Work performed on ALS Beamline 8.2.1.

Citation: A. Laganowsky, C. Liu, M.R. Sawaya, J.P. Whitelegge, J. Park, M. Zhao, A. Pensalfini, A.B. Soriaga, M. Landau, P.K. Teng, D. Cascio, C. Glabe, D. Eisenberg, "Atomic View of a Toxic Amyloid Small Oligomer," Science 335 (6073), 1228-1231.