title: Structural Studies of Amyloid Proteins at the Molecular Level.
abstract: Dozens of proteins are known to convert to the aggregated amyloid state. These include fibrils associated with systemic and neurodegenerative diseases and cancer, functional amyloid fibrils in microorganisms and animals, and many denatured proteins. Amyloid fibrils can be much more stable than other protein assemblies. In contrast to globular proteins, a single protein sequence can aggregate into several distinctly different amyloid structures, termed polymorphs, and a given polymorph can reproduce itself by seeding. Amyloid polymorphs may be the molecular basis of prion strains. Whereas the Protein Data Bank contains some 100,000 globular protein and 3,000 membrane protein structures, only a few dozen amyloid protein structures have been determined, and most of these are short segments of full amyloid-forming proteins. Regardless, these amyloid structures illuminate the architecture of the amyloid state, including its stability and its capacity for formation of polymorphs.
authors.affiliation: Howard Hughes Medical Institute and Molecular Biology Institute, University of California, Los Angeles, California 90095-1570; email: david@mbi.ucla.edu , sawaya@mbi.ucla.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Eisenberg
authors.affiliation: Howard Hughes Medical Institute and Molecular Biology Institute, University of California, Los Angeles, California 90095-1570; email: david@mbi.ucla.edu , sawaya@mbi.ucla.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Sawaya
mesh_terms: D020816:Amino Acid Motifs; D058227:Amyloidogenic Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D020285:Cryoelectron Microscopy; D015870:Gene Expression; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D000072002:Prion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D066263:Protein Aggregation, Pathological / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011489:Protein Denaturation; D055503:Protein Multimerization; D055550:Protein Stability; D017433:Protein Structure, Secondary; D014961:X-Ray Diffraction
chemical_list: D058227:Amyloidogenic Proteins; D000072002:Prion Proteins
keywords: X-ray diffraction; amyloid symmetry; cryo-EM; cryo–electron microscopy; polymorphs; solid-state nuclear magnetic resonance; ssNMR; steric zipper