Atomic View of a Toxic Amyloid Small Oligomer

Journal Article · Mon Apr 30 04:00:00 EDT 2012 · Science

DOI:https://doi.org/10.1126/science.1213151· OSTI ID:1037487

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 ^[1]

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1. UCI

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 {alpha}{beta} crystallin, which forms an oligomeric complex exhibiting properties of other amyloid oligomers: {beta}-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 {beta}-amyloid protein of Alzheimer's disease. Cylindrins offer models for the hitherto elusive structures of amyloid oligomers.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: NSFUNIVERSITYNIHHHMI
• OSTI ID: 1037487
• Journal Information: Science, Journal Name: Science Journal Issue: 03, 2012 Vol. 335; ISSN 0036-8075
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
DISEASES
PROTEINS
TRANSIENTS