Atomic view of a toxic amyloid small oligomer.

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.

• Authors: Arthur Laganowsky, Cong Liu, Michael R Sawaya, Julian P Whitelegge, Jiyong Park, Minglei Zhao, Anna Pensalfini, Angela B Soriaga, Meytal Landau, Poh K Teng, Duilio Cascio, Charles Glabe, David Eisenberg
• Journal: Science (New York, N.Y.) (Science) Vol. 335 Issue 6073 Pg. 1228-31 (Mar 09 2012) ISSN: 1095-9203 [Electronic] United States
• PMID: 22403391 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Amyloid
• Amyloid beta-Peptides
• Antibodies
• Peptide Fragments
• Recombinant Proteins
• alpha-Crystallin B Chain

Topics

• Amino Acid Sequence
• Amyloid (chemistry, immunology)
• Amyloid beta-Peptides (chemistry)
• Antibodies (immunology)
• Crystallography, X-Ray
• Hydrogen Bonding
• Models, Molecular
• Molecular Dynamics Simulation
• Molecular Sequence Data
• Peptide Fragments (chemistry, immunology)
• Protein Conformation
• Protein Structure, Tertiary
• Recombinant Proteins (chemistry)
• alpha-Crystallin B Chain (chemistry, immunology)