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The Amyloid State of Proteins
Author(s) -
Eisenberg David,
Sawaya Michael,
Nelson Rebecca,
Soragni Alice,
Rodriguez Jose,
Jiang Lin,
Sangwan Smriti,
Johnson Lisa,
Laganowsky Arthur,
Liu Cong,
Soriaga Angela,
Landau Meytal,
Cascio Duilio,
Sievers Stuart,
SaelicesGomez Lorena,
Guenther Elizabeth,
Hughes Michael
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.218.1
Subject(s) - antiparallel (mathematics) , oligomer , fibril , amyloid (mycology) , amyloid fibril , biophysics , amyloid disease , chemistry , biochemistry of alzheimer's disease , crystallography , amyloid β , biochemistry , alzheimer's disease , biology , amyloid precursor protein , medicine , pathology , disease , polymer chemistry , inorganic chemistry , physics , quantum mechanics , magnetic field
Amyloid diseases, including Alzheimer's, Parkinson's, and the prion conditions, are each associated with a particular protein in fibrillar form. At the morphological level, these fibers appear similar and are termed “amyloid.” From x‐ray and electron diffraction, we found that the adhesive segments of amyloid fibers are short protein sequences which form pairs of interdigitated, in‐register beta sheets. These amyloid fibrils were long suspected to be the disease agents, but evidence suggests that in at least some of the neurodegenerative diseases, smaller, often transient and polymorphic oligomers are the toxic entities. In attempts to determine structures for such oligomers, we have discovered segments of amyloid‐forming proteins that form toxic, antiparallel beta, out‐of‐register structures. In one case, the oligomer is a cylindrical barrel, formed from six anti‐parallel, out‐of‐register protein strands, which we term a cylindrin. In another case, the oligomer is an open, continuous cylindrin‐like structure that we term a corkscrew. Cylindrins offer models for the hitherto elusive structures of amyloid oligomers, and are distinct in structure from amyloid fibrils. From the known structure of the spine of an amyloid fibril, we find it is possible to design an inhibitor of fibril formation.