Yoshitaka Ishii


Website: Ishii's Group Page


Born 1968; BS, Kyoto University Japan, 1992; PhD, Kyoto University, Japan, 1997; Research Fellow of the Japan Society for the Promotion of Science (JSPS), 1996-1998; Research Fellow of the National Institutes of Health, Maryland, 1998-2001.

We focus on developments of novel solid-state NMR (SSNMR) methods and applications of the improved methods to elucidate structures of interesting biomolecules. SSNMR has provided unique structural information such as atomic-level structures and structural disorder for a variety of materials. Especially, its applications to bio-supramolecular complexes such as membrane bound proteins and amyloidogenic proteins in fibrils have attracted great interest because many of their structures have been inaccessible by traditional approaches such as X-ray diffraction or liquid state NMR, owing to their size, limited solubility, and difficulties in crystallization. Our group aims to play a leading role at the rapid developmental stage of SSNMR on biomolecules. We also stress characterization of structures of biomedically and chemically important molecules that cannot be probed with other analytical methods. Naturally, our research is transdisciplinary between chemistry, physics, and biology or between analytical chemistry, spectroscopy, and structural biology. Some examples of ongoing research projects are as follows:

Structures of neurodegenarative disease peptides by NMR

Alzheimer's �-amyloid (A�) peptide fibrils are major components of amyloid plaques found in brains of patients affected by Alzheimer's disease, and have been considered to be major suspects of the tragic disease. Surprisingly little has been experimentally known on the structure of the peptides in fibrils. Recently, we demonstrated the first site-resolved conformations of A� peptides in a fibrillized state for a multiply 13C labeled sample, based on an empirical relationship between 13C chemical shifts and peptide conformations. We are developing tailor-made SSNMR methods to reveal its unknown tertiary structure, which may be significant for discovery of cures for the disease. The developed methods can be applied to the peptides related to other neurodegenerative diseases such as Parkinson's disease and mad cow disease.

Developments of SSNMR methods: More sensitivity and more information

We recently demonstrated that 1H detected NMR enhances sensitivity of 13C and 15N SSNMR, which is an essential tool for studies on general organic materials including biomolecules by a factor of up to 5 under very fast sample spinning (30 kHz) in an ultra high-field (17 T). Because required experimental time is proportional to the square of sensitivity, 1H detected SSNMR dramatically speeds up our experiments. Although 1H detected NMR has been rarely used for these three decades, this method may completely change the way of SSNMR in the near future. Our group also works on developing methods to elucidate more structural constraints using uniformly or multiply labeled proteins/peptides.

Two-dimensional 13C/13C exchange solid-state NMR spectrum of fibrillized Alzheimer's �-amyloid peptide fragments (16-22 residue: KLVFFAE) uniformly 13C- and 15N-labeled from L17 though A21. Assignments of the signals are given in the figure. Analysis of spectral line widths and chemical shifts demonstrates well ordered structures and �-sheet formation all through the molecule.
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