Solid-State NMR Studies Reveal Native-like ?-Sheet Structures in Transthyretin Amyloid.

ABSTRACT: Structural characterization of amyloid rich in cross-? structures is crucial for unraveling the molecular basis of protein misfolding and amyloid formation associated with a wide range of human disorders. Elucidation of the ?-sheet structure in noncrystalline amyloid has, however, remained an enormous challenge. Here we report structural analyses of the ?-sheet structure in a full-length transthyretin amyloid using solid-state NMR spectroscopy. Magic-angle-spinning (MAS) solid-state NMR was employed to investigate native-like ?-sheet structures in the amyloid state using selective labeling schemes for more efficient solid-state NMR studies. Analyses of extensive long-range (13)C-(13)C correlation MAS spectra obtained with selectively (13)CO- and (13)C?-labeled TTR reveal that the two main ?-structures in the native state, the CBEF and DAGH ?-sheets, remain intact after amyloid formation. The tertiary structural information would be of great use for examining the quaternary structure of TTR amyloid.

SUBMITTER: Lim KH 

PROVIDER: S-EPMC5035109 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature