Title
Solid-State NMR Studies Reveal Native-like β-Sheet Structures in Transthyretin Amyloid
Author
Kwang Hun Lim, Anvesh K. R. Dasari, Ivan Hung, Zhehong Gan, Jeffery W. Kelly, Peter E. Wright, David E. Wemmer
Year
2016
Journal
Biochemistry
Abstract
Structural characterization of amyloid rich in cross-β 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 β-sheet structure in noncrystalline amyloid has, however, remained an enormous challenge. Here we report structural analyses of the β-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 β-sheet structures in the amyloid state using selective labeling schemes for more efficient solid-state NMR studies. Analyses of extensive long-range 13C–13C correlation MAS spectra obtained with selectively 13CO- and13Cα-labeled TTR reveal that the two main β-structures in the native state, the CBEF and DAGH β-sheets, remain intact after amyloid formation. The tertiary structural information would be of great use for examining the quaternary structure of TTR amyloid.
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Biochemistry