Format

Send to

Choose Destination
Science. 2012 Mar 9;335(6073):1228-31. doi: 10.1126/science.1213151.

Atomic view of a toxic amyloid small oligomer.

Author information

1
Department of Biological Chemistry, University of California Los Angeles (UCLA), Howard Hughes Medical Institute (HHMI), Los Angeles, CA 90095, USA.

Abstract

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 suggests that smaller, often transient and polymorphic oligomers are the toxic entities. Here, we 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, that we term a cylindrin. The cylindrin structure is compatible with a sequence segment from the β-amyloid protein of Alzheimer's disease. Cylindrins offer models for the hitherto elusive structures of amyloid oligomers.

PMID:
22403391
PMCID:
PMC3959867
DOI:
10.1126/science.1213151
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center