title: Detection of Helical Intermediates During Amyloid Formation by Intrinsically Disordered Polypeptides and Proteins.
abstract: Amyloid formation and aberrant protein aggregation are hallmarks of more than 30 different human diseases. The proteins that form amyloid can be divided into two structural classes: those that form compact, well-ordered, globular structures in their unaggregated state and those that are intrinsically disordered in their unaggregated states. The latter include the Aβ peptide of Alzheimer's disease, islet amyloid polypeptide (IAPP, amylin) implicated in type 2 diabetes and α-synuclein, which is linked to Parkinson's disease. Work in the last 10 years has highlighted the potential role of pre-amyloid intermediates in cytotoxicity and has focused attention on their properties. A number of intrinsically disordered proteins appear to form helical intermediates during amyloid formation. We discuss the spectroscopic methods employed to detect and characterize helical intermediates in homogenous solution and in membrane-catalyzed amyloid formation, with the emphasis on the application of circular dichroism (CD). IAPP is used as an example, but the methods are generally applicable.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Diabetes Research Program, NYU School of Medicine, 550 First Avenue, Smilow 906, New York, NY, 10016, USA. Andisheh.Abedini@nyumc.org.
authors.forename: Andisheh
authors.initials: A
authors.lastname: Abedini
authors.affiliation: Structural Biology Program, Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, NY, 10016, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Cao
authors.affiliation: Department of Chemistry, Stony Brook University, 647 Chemistry, Stony Brook, NY, 11794-3400, USA. daniel.raleigh@stonybrook.edu.|Graduate Program in Biochemistry and Structural Biology, Stony Brook University, Stony Brook, NY, 11794-3400, USA. daniel.raleigh@stonybrook.edu.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Raleigh
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D058227:Amyloidogenic Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D008967:Molecular Biology / Q000379:methods*; D066263:Protein Aggregation, Pathological; D051844:alpha-Synuclein / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification
chemical_list: D058227:Amyloidogenic Proteins; D064267:Intrinsically Disordered Proteins; D051844:alpha-Synuclein
keywords: Amylin; Amyloid; Aβ; CD; Helical intermediate; Islet amyloid polypeptide; Oligomer