title: Dynamic domains of amyloid fibrils can be site-specifically assigned with proton detected 3D NMR spectroscopy.
abstract: Several amyloid fibrils have cores framed by highly dynamic, intrinsically disordered, domains that can play important roles for function and toxicity. To study these domains in detail using solid-state NMR spectroscopy, site-specific resonance assignments are required. Although the rapid dynamics of these domains lead to considerable averaging of orientation-dependent NMR interactions and thereby line-narrowing, the proton linewidths observed in these samples is far larger than what is regularly observed in solution. Here, we show that it is nevertheless possible to record 3D HNCO, HNCA, and HNcoCA spectra on these intrinsically disordered domains and to obtain site-specific assignments.
authors.affiliation: Department of Biochemistry and Molecular Medicine, Zilkha Neurogenetic Institute, Keck School of Medicine of USC, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Falk
authors.affiliation: Department of Biochemistry and Molecular Medicine, Zilkha Neurogenetic Institute, Keck School of Medicine of USC, 1501 San Pablo St, Los Angeles, CA, 90033, USA. asiemer@usc.edu.
authors.forename: Ansgar B
authors.identifier: 0000-0003-0901-011X
authors.initials: AB
authors.lastname: Siemer
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D064267:Intrinsically Disordered Proteins / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011487:Protein Conformation; D000072417:Protein Domains; D011522:Protons
chemical_list: D000682:Amyloid; D064267:Intrinsically Disordered Proteins; D011522:Protons
keywords: Amyloid fibrils; Intrinsically disordered domains; Resonance assignment; Solid-state NMR