title: Solid-State NMR Studies Reveal Native-like β-Sheet Structures in Transthyretin Amyloid.
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 (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.
authors: Department of Chemistry, East Carolina University , Greenville, North Carolina 27858, United States.
authors: Kwang Hun
authors: KH
authors: Lim
authors: Department of Chemistry, East Carolina University , Greenville, North Carolina 27858, United States.
authors: Anvesh K R
authors: AK
authors: Dasari
authors: Center of Interdisciplinary Magnetic Resonance (CIMAR), National High Magnetic Field Laboratory (NHMFL) , 1800 East, Paul Dirac Drive, Tallahassee, Florida 32310, United States.
authors: Ivan
authors: I
authors: Hung
authors: Center of Interdisciplinary Magnetic Resonance (CIMAR), National High Magnetic Field Laboratory (NHMFL) , 1800 East, Paul Dirac Drive, Tallahassee, Florida 32310, United States.
authors: Zhehong
authors: Z
authors: Gan
authors: Jeffery W
authors: JW
authors: Kelly
authors: Peter E
authors: PE
authors: Wright
authors: Department of Chemistry, University of California , Berkeley, California 94720, United States.
authors: David E
authors: DE
authors: Wemmer
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D011228:Prealbumin / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D000682:Amyloid; D011228:Prealbumin