25-30 August 2019
Henry Ford Building
Europe/Berlin timezone

Sensitivity-Enhanced Protein Solid-state NMR using Ultra-fast MAS and Structural Studies of Alzheimer’s Amyloid-β

29 Aug 2019, 11:05
Lecture Hall C (Henry Ford Building)

Lecture Hall C

Henry Ford Building

Talk Biological applications Biomolecules


Dr Yoshitaka Ishii (Tokyo Institute of Technology)


This work involves two separate topics on our ongoing progress of protein SSNMR methods using ultra-fast MAS and solid-state NMR (SSNMR) applications to amyloid proteins. First, we discuss resolution and sensitivity enhancement in 1H-detected biomolecular SSNMR under ultra-fast magic angle spinning (UFMAS) conditions (≥ 80 kHz) in a high magnetic field (1H frequency: 750-900 MHz).1,2 Our data on protein microcrystal GB1 and amyloid-β (Aβ) fibril show that traditionally time-consuming 3-5D biomolecular SSNMR is feasible for signal assignments and structural examination of proteins in a nano-mole-scale with this approach. Our discussion will include drastic sensitivity enhancement by novel polarization-transfer schemes and other methods for multi-dimensional SSNMR using ultra-fast MAS. We briefly introduce our nation-wide effort to construct a 1.3 GHz NMR at RIKEN.

Second, we examine structures, kinetics, and functions of amyloid-β using solid-state NMR (SSNMR). Increasing evidence suggests that formation and propagation of misfolded aggregates of 42-residue Aβ42, rather than the more abundant 40-residue Aβ40, provokes the Alzheimer’s cascade. Our group recently presented the first detailed atomic model of Aβ42 amyloid fibril based on SSNMR data.3 The result revealed a unique structure that was not previously identified for Aβ40 fibril. Based on the results and additional SSNMR data, we discuss how amyloid fibril structures affect “prion-like” propagation across different Aβ isoforms, including WT Aβ40 and E22G pathogenic mutant of Aβ40.4 We also discuss SSNMR-based structural analysis of toxic spherical assembly of Aβ, including one that was identified from brains affected by AD.5 The results provide insight into amyloid misfolding of Aβ42 in Alzheimer’s disease.

(1) Wickramasinghe, N.et al. Nat. Methods 2009, 6, 215.
(2) Ishii, Y.et al. J. Magn. Reson. 2018, 286, 99.
(3) Xiao, Y.et al. Nat. Struct. Mol. Biol. 2015, 22, 499.
(4) Yoo, B.et al. JACS 2018, 140, 2781.
(5) Parthasarathy, S.et al. JACS 2015, 137, 6480.

Primary authors

Dr Yoshitaka Ishii (Tokyo Institute of Technology) Dr Takayuki Kamihara (Tokyo Institute of Technology) Mr Isamu Matsuda (Tokyo Institute of Technology) Dr Yiling Xiao (Univ. Illinois at Chicago)

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