title: Protein misfolded oligomers: experimental approaches, mechanism of formation, and structure-toxicity relationships.
abstract: The conversion of proteins from their native state to misfolded oligomers is associated with, and thought to be the cause of, a number of human diseases, including Alzheimer's disease, Parkinson's disease, and systemic amyloidoses. The study of the structure, mechanism of formation, and biological activity of protein misfolded oligomers has been challenged by the metastability, transient formation, and structural heterogeneity of such species. In spite of these difficulties, in the past few years, many experimental approaches have emerged that enable the detection and the detailed molecular study of misfolded oligomers. In this review, we describe the basic and generic knowledge achieved on protein oligomers, describing the mechanisms of oligomer formation, the methodologies used thus far for their structural determination, and the structural elements responsible for their toxicity.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. fb330@cam.ac.uk
authors.forename: Francesco
authors.initials: F
authors.lastname: Bemporad
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Chiti
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D002623:Chemistry Techniques, Analytical; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D011487:Protein Conformation; D017510:Protein Folding; D055503:Protein Multimerization
chemical_list: D000682:Amyloid