Open AccessSolid-State NMR Studies Reveal Native-like β-Sheet Structures in Transthyretin Amyloid
Author(s) -
Kwang Hun Lim,
Anvesh K. R. Dasari,
Ivan Hung,
Zhehong Gan,
Jeffery W. Kelly,
Peter E. Wright,
David E. Wemmer
Publication year - 2016
Publication title -
biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.43
H-Index - 253
eISSN - 1520-4995
pISSN - 0006-2960
DOI - 10.1021/acs.biochem.6b00649
Subject(s) - amyloid (mycology) , solid state nuclear magnetic resonance , transthyretin , chemistry , nuclear magnetic resonance spectroscopy , amyloid disease , congo red , beta sheet , amyloid fibril , protein structure , protein secondary structure , protein folding , crystallography , stereochemistry , biochemistry , nuclear magnetic resonance , biology , amyloid β , organic chemistry , pathology , medicine , inorganic chemistry , physics , disease , adsorption , endocrinology
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 (13)C-(13)C correlation MAS spectra obtained with selectively (13)CO- and (13)Cα-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.