Structural Changes Associated with Transthyretin Misfolding and Amyloid Formation Revealed by Solution and Solid-State NMR
Year: 2016
Type: article
Abstract: Elucidation of structural changes involved in protein misfolding and amyloid formation is crucial for unraveling the molecular basis of amyloid formation. Here we report structural analyses of the amyloidogenic intermediate and amyloid aggregates of transthyretin using solution and solid-state nuclear magnetic resonance (NMR) spectroscopy. Our solution NMR results show that one of the two main β-sheet structures (CBEF β-sheet) is maintained in the aggregation-competent intermediate, while the other DAGH β-sheet is more flexible on millisecond time scales. Magic-angle-spinning solid-state NMR revealed that AB loop regions interacting with strand A in the DAGH β-sheet undergo conformational changes, leading to the destabilized DAGH β-sheet.
Source: Biochemistry
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, National High Magnetic Field Laboratory, National Institutes of Health, National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, Division of Materials Research, High Magnetic Field Laboratory, Chinese Academy of Sciences
Awards: Mechanistic studies of transthyretin misfolding and amyloid formation through a c, G1800297237, G1923085470, G2294341347, G2386482098, G4624992917, G502626589, National High Magnetic Field Laboratory Renewal 2013-2017, Molecular Pathogenesis of Age-Dependent CNS Regeneration, G7444057152, Probing the biochemical mechanism of amyloid disease, G9000003207, G9000245748, Probing the biochemical mechanism of amyloid disease
OpenAlex ID: W2309468815