Home ＞GCOE Researchers ＞Yuichiro MAEDA

GCOE Researchers

Yuichiro MAEDA

Affiliation
/Position		 Graduate School of Science, Structural Biology Research Center, Center Director; Division of Biological Science, Professor
Doctorate Doctor of Science
Research interests Structural biology, Calcium regulation mechanism in muscle contraction, actin filament dynamics
address ymaeda＠spring8.or.jp
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+81-52-788-6228
  Laboratory

Outline of research

To elucidate the mechanism of calcium regulation in muscle contraction, we have been studying the structure of the actin filament (actin + tropomyosin + troponin complex). In 1979-1989, while I undertook the responsibility for construction and operation of a beamline at European Molecular Biology Lab (EMBL) in Hamburg, we revealed a structural change of the actin filament by observing changes in X-ray diffraction intensity in contracting living muscle. Based on these results, we concluded that changes in both calcium binding and myosin interaction contribute to this structural change.

In 1990, we decided that it is necessary to understand the structure of the actin filament at an atomic resolution, and initiated a crystallographic study of troponin, which plays the central role in the actin filament-based muscle regulation. We used recombinant DNA techniques to express all three proteins and reconstruct the complex. In 2003, we succeeded in obt aining the crystal structure of troponin, and discovered a molecular switch that is activated by calcium binding. This result was attained 38 years after the discovery of troponin by Ebashi in 1965; our project itself spanned 12 years.

From 2003, our project was adopted by the ERATO (Exploratory Research for Advanced Technology) project of the Japan Science and Technology Agency. At that time, we expanded our focus from the individual constituent molecules to the entire complex. Our aims are to elucidate the crystal structure of the entire actin filament complex (integrated structural biology), to comprehensively understand the structural dynamics within the troponin molecule, and to correlate this understanding with its function (dynamic structural biology). We have also revealed the crystal structures of CapZ and tropomodulin, and electron-microscopic structures of CapZ binding at the end of the actin filament. Based on these structures, we have elucidated the mechanism of suppression of polymerization/depolymerization at the end of the filament. We have successfully obtained an atomic model of the actin polymer that enables us not only to explain all the previous biochemical results but also to propose hypothesis regarding its structure and dynamics; we have begun to test this hypothesis with mutated actins, using the first established actin expression system. Over the course of our studies, our laboratory has succeeded in developing a broad range of techniques, including expression method for large complex, structural analysis techniques for filamentous aggregates, and image analysis algorithm for electron cryo-microscopic images; taken together, this wide expertise makes our group one of the world's leading laboratories in the field of structural biology of filamentous aggregates. Muscle is one of the rare systems that allow direct correlation of knowledge at the protein level with quantitative organic parameters such as developed tension, contraction rate and thermogenesis. In that context, studies on muscle have led the way in integrated systems biology. In the future, we seek to further correlate changes in the atomic structure of proteins with their organic functions and parameters.

References

  1. Oda T. et al. (2008) The nature of the G- to F-actin transition. Nature, in press.
  2. Iwasa M. et al. (2008) Dual roles of Gln137 of actin revealed by recombinant human cardiac muscle -actin Mutants. J. Biol. Chem., 283: 21045-53.
  3. Minakata S. et al. (2008) Two crystal structures of tropomyosin C-terminal fragment 176-273: exposure of the hydrophobic core to the solvent destabilizes the tropomyosin molecule. Biophys. J., 95: 710-719.
  4. Popp D. et al. (2008) Molecular structure of the ParM polymer and the mechanism leading to its nucleotide driven dynamic instability. EMBO J., 27: 570-579.
  5. Narita A. et al. (2007) Molecular determination by electron microscopy of the dynein-microtubule complex structure. J. Mol. Biol., 372: 1320-1336.
  6. Narita A　& Maeda Y. (2007) Molecular determination by electron microscopy of the actin filament end structure. J. Mol. Biol., 365: 480-501.
  7. Narita A et al. (2006) Structural basis of actin filament capping at the barbed-end: a cryo-electron microscopy study. EMBO J., 25: 5626-33.
  8. Imai H et al. (2006) Two-dimensional Averaged Images of the Dynactin Complex Revealed by Single Particle Analysis. J. Mol. Biol., 359: 833-839.
  9. Takeda S. et al. (2003) Crystal structure of the core domain of human cardiac troponin in the Ca2+-saturated form. Nature, 424: 35-41.
  10. Yamashita A. et al. (2003) Crystal Structure of CapZ: structural basis for actin filament barbed end capping. EMBO J., 22: 1529-1538.

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