Elucidation of dynamics of biomolecules by exploiting ultra-high field NMR spectroscopy
A wide variety of biomacromolecules have adopted their own three-dimensional structures with complexity and exquisiteness during the long evolution history and thereby become able to express sophisticated functions such as strict and flexible molecular recognition and efficient and specific catalysis in the biological systems. Many of the biomolecules form supermolecular machines through specific intermolecular interactions and thereby express their own biological functions. The biomacromolecules making up these machineries exhibit molecular motions on varying spatial and time scales. To better understand the molecular basis of the mechanisms underlying the higher biological functions, it is therefore essential to elucidate dynamic properties of biomolecules and their assemblies. For instance, sugar chains, our major research subjects, which are called the third biological chains after nucleic acids and proteins, form glycoconjugates with proteins and lipids and thereby play crucial roles in a variety of biological systems. The sugar chains form supermolecular clusters on cell surfaces, which offer unique platforms of molecular recognition events mediating cell-cell communication. Growing evidence has also indicated that the sugar chains modify proteins and thereby control their functions and fates. However, the sugar chains have significant degrees of heterogeneities of chemical structures and freedoms in internal motions, which have so far hampered molecular science approaches. Our biomolecular studies are based on detailed analyses of structures and dynamics of various biological macromolecules including proteins and glycoconjugates and their complexes at atomic level, primarily using ultra-high field nuclear magnetic resonance (NMR) spectroscopy. In particular, we conducted studies aimed at elucidating dynamical structures of sugar chains and proteins for integrative understanding of the mechanisms underlying their biological functions. For this purpose, we use versatile approaches on the basis of molecular and cellular biology and nanoscience along with molecular spectroscopy.
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- "Molecular basis of sugar recognition by the human L-type lectins ERGIC-53, VIPL and VIP36" J. Biol. Chem. 283, 1857-1861 (2008)
- "Direct interactions between NEDD8 and ubiquitin E2 conjugating enzymes upregulate cullin-based E3 ligase activity" Nature Struct. Mol. Biol. 14, 167-168 (2007)
- "Structural views of glycoprotein-fate determination in cells" Glycobiology, 17, 1031-1044 (2007)