Laboratories

Structural Biology

Prof. Hakoshima
Professor
Toshio HAKOSHIMA
Assistant Professor
Ken KITANO, Tomoyuki MORI
Labs HP
http://bsw3.naist.jp/hako/

Outline of Research and Education

Proteins are folded into specific three dimensional (3D) structures, which are essential for imparting functions such as molecular recognition and catalysis. Without precise knowledge of their 3D-structures, we are unable to understand how proteins execute their respective molecular functions and, in turn, unable to rationally design inhibitors or drugs. Thus, the experimental determination of protein 3D-structures represents the hallmark of structural biology. Structural biology in our laboratory is performed using X-ray crystallography to determine the 3D-structures of proteins and molecular complexes at atomic resolution, and biochemical/biophysical analyses are performed to delineate the mechanisms by which proteins function at the atomic, molecular, and cellular levels.

Our overall goal is to contribute to the understanding of the nature of life. Our long-term objective is to understand the molecular functions of proteins and other biological macromolecules and their complexes in terms of molecular structures. Our efforts are directed towards defining the manner by which protein interactions and 3D-structures determine specificity and how structural changes enable functional switches in living cells.

We expect our lab to be an international one and we welcome foreign students to study protein structures and functions with us.

Major Research Topics

Structural molecular medicine

Drug-target proteins and other proteins important in medical research such as cancer, teratogenesis and infectious diseases

Structural cell biology

G proteins, and their regulators and effectors, which play central roles in intracellular signal transduction that regulate cell motility with rearrangement of the cytoskeleton and cell adhesion

Structural molecular biology

Enzyme engineering in biodegradable plastic synthesis

Structural plant biology

Proteins that play pivotal roles in plant hormone signaling, such as receptors and master regulators

References

  1. Hirano et al., Nature Plants. 17; 3:17010, 2017
  2. Chamberlain et al., Nature Struct. Mol. Biol., 21, 803–809. 2014
  3. Hirano et al., EMBO J., 30, 2734-2747, 2011
  4. Terawaki et al., EMBO J., 29, 236-250, 2010
  5. Murase et al., Nature, 456, 459-463, 2008
  6. Yamaguchi et al., Structure, 14, 589-600, 2006
  7. Sakurai et al., EMBO J., 24, 683-693, 2005
  8. Hamada et al., EMBO J., 22, 502-514, 2003
  9. Fujii et al., Nature Struct. Biol., 7, 889-893, 2000
  10. Hamada et al., EMBO J., 19, 4449-4462, 2000
  11. Maesaki et al., Mol Cell, 4, 793-803, 1999
  12. Kato et al., Cell, 88, 717-723, 1997
Fig.1
Fig.1 A crystal of histidine protein phosphatase (left) crystallized in our laboratory and part of its electron density map at 1.9 Å resolution obtained from X-ray crystal structure analysis
Fig.2
Fig.2 The SPring-8 synchrotron radiation facilities at Harima, Hyogo. We perform X-ray intensity data collection at SPring-8 for structure determination.
Fig.3
Fig.3 The ternary complex of gibberellin (space-filled model in while and red)-bound receptor GID1 (blue and cyan) trapping its downstream effector protein DELLA protein (pink) from our recent Nature article [5].
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