Atomic View of a Toxic Amyloid Small Oligomer

Amyloid diseases, including Alzheimer's, Parkinson's, and the priori 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 oligomer...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2012-03, Vol.335 (6073), p.1228-1231
Main Authors: Laganowsky, Arthur, Liu, Cong, Sawaya, Michael R., Whitelegge, Julian P., Park, Jiyong, Zhao, Minglei, Pensalfini, Anna, Soriaga, Angela B., Landau, Meytal, Teng, Poh K., Cascio, Duilio, Glabe, Charles, Eisenberg, David
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
alpha-Crystallin B Chain - chemistry
alpha-Crystallin B Chain - immunology
Alzheimers Disease
Amino Acid Sequence
Amyloid - chemistry
Amyloid - immunology
Amyloid beta-Peptides - chemistry
Amyloids
Antibodies
Antibodies - immunology
BASIC BIOLOGICAL SCIENCES
Biochemistry
Biological and medical sciences
Brain
Crystal structure
Crystallography, X-Ray
DISEASES
Free energy
Fundamental and applied biological sciences. Psychology
Hydrogen Bonding
Hydrogen bonds
Models, Molecular
Molecular biophysics
Molecular Dynamics Simulation
Molecular Sequence Data
Neurodegeneration
Oligomers
Peptide Fragments - chemistry
Peptide Fragments - immunology
Protein Conformation
Protein Structure, Tertiary
PROTEINS
Recombinant Proteins - chemistry
Solar fibrils
Structure in molecular biology
TRANSIENTS
Tridimensional structure
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Summary:Amyloid diseases, including Alzheimer's, Parkinson's, and the priori 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 ccB crystallin, which forms an oligomeric complex exhibiting properties of other amyloid oligomers: ß-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 ß-amyloid protein of Alzheimer's disease. Cylindrins offer models for the hitherto elusive structures of amyloid oligomers.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1213151