Atomic View of a Toxic Amyloid Small Oligomer

• Published in: Science (American Association for the Advancement of Science) Vol. 335; no. 6073; pp. 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: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 09-03-2012; The American Association for the Advancement of Science
• 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; Nervous system diseases; Alzheimer disease; Central nervous system disease; Degenerative disease; Amyloid; Oligomer; Secondary structure; Cerebral disorder
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1213151

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.