title: Determination of amyloid core structure using chemical shifts.
abstract: Amyloid fibrils are the pathological hallmark of a large variety of neurodegenerative disorders. The structural characterization of amyloid fibrils, however, is challenging due to their non-crystalline, heterogeneous, and often dynamic nature. Thus, the structure of amyloid fibrils of many proteins is still unknown. We here show that the structure calculation program CS-Rosetta can be used to obtain insight into the core structure of amyloid fibrils. Driven by experimental solid-state NMR chemical shifts and taking into account the polymeric nature of fibrils CS-Rosetta allows modeling of the core of amyloid fibrils. Application to the Y145X stop mutant of the human prion protein reveals a left-handed β-helix.
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, Göttingen, Germany.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Skora
authors.forename: Markus
authors.initials: M
authors.lastname: Zweckstetter
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017354:Point Mutation; D011328:Prions / Q000737:chemistry* / Q000235:genetics; D017433:Protein Structure, Secondary; D012984:Software
chemical_list: D000682:Amyloid; D011328:Prions