Laboratory of Protein Synthesis and Expression

Member

Director Junichi TAKAGI
Associate Professor Kenji IWASAKI
Assistant Professor Yu KITAGO
Takao ARIMORI
Naoyuki MIYAZAKI
Technical Staff Keiko KAWAKAMI

 

Correspondence

Tel 81-6-6879-8607
Fax 81-6-6879-8609
E-mail
URL http://www.protein.osaka-u.ac.jp/rcsfp/synthesis/index.html

Research

Cellular response to the extracellular environment depends on the “sensing” the extracellular cues by use of the receptor-ligand system. Binding of ligands to the extracellular domain of the receptors transduce signals into cells that initiates various cellular events, ultimately changing the cell fate. In spite of a wealth of cell biological “signal transduction researches” conducted at every corner of today’s biomedical arena, mechanism for the “signal transmission across the membrane”, the very first step in the signaling pathway is poorly understood. Our study focuses on questions such as how receptors recognize their specific ligands, how this recognition leads to structural change in the receptor complex, and how the information cross the plasma membrane without transporting chemical entity. Using structural as well as chemical approach, we would tackle on this difficult problem to obtain insights into the mechanism of transmembrane signaling.

fig.1_bunshisosei
Fig. 1: Crystal structure of SORLA Vps10p domain implicated in the intracellular trafficking of amyloidogenic peptides
fig.2_bunshisosei
Fig. 2: 2-D Hybrid method; deformed structures are calculated and fitted into 2-D EM images.

Current Research Programs

  1. Structure and function of extracellular ligands and their receptors implicated in cell adhesion and neural guidance/morphogenesis.
  2. Structure-guided molecular design of novel proteins.
  3. "Correlative" structural analysis by multidisciplinary approach.
  4. Development of high-quality recombinant protein production system.
  5. 3-D visualization of conformationally heterogeneous macromolecules using electron microscopy.

References

  1. PA tag: a versatile protein tagging system using a super high affinity antibody against a dodecapeptide derived from human podoplanin. Fujii, Y., et al. (2014) Protein Exp. Purif. 95, 240-247.
  2. Novel role for SORLA/SORL1 as lysosomal sorting receptor for amyloid-β peptide is impaired by familial Alzheimer disease mutation. Caglayan S, T et al. (2014) Science Transl. Med., 6, 223ra20.
  3. A multi-purpose fusion tag derived from an unstructured and hyper-acidic region of the amyloid precursor protein. Sangawa T, et al (2013) Protein Sci., 22., 840-850.
  4. A point mutation in Semaphorin 4A associates with defective endosomal sorting and causes retinal degeneration. Nojima S, et al. (2013) Nature Commun. 4:1406.