Research Activities
A Unique Leucine-Valine Adhesive Motif Supports Structure and Function of Protein Disulfide...

  The endoplasmic reticulum (ER) in the cell has a mechanism to introduce disulfide bonds into newly created proteins to stabilize their structure. Although P5, one of the PDI family enzymes, has been reported to be involved in various physiological functions, such as cancer and other diseases, endoplasmic reticulum stress response, and blood coagulation, the detailed mechanism has not been fully understood due to its unknown overall structure.

 A research group consisting of Assistant Professor Masaki Okumura (Frontier Research Institute for Interdisciplinary Sciences, Tohoku University); Assistant Professor Shingo Kanemura (currently at the School of Science and Technology, Kwansei Gakuin University); Assistant Professor Motonori Matsusaki (currently at the Institute for Enzyme Research, University of Tokushima); Professor Kenji Inaba (Graduate School of Life Science and the Department of Chemistry and Graduate School of Science, Tohoku University); Professor Tomohide Saio (Institute for Enzyme Research, University of Tokushima); Professor Young-Ho Lee at the Korea Basic Science Institute; and Professor Shuji Akiyama at the Institute for Molecular Science, National Institutes of Natural Sciences, has discovered by a combination of X-ray crystallography and small-angle X-ray scattering (SAXS) that P5 adopts a dimeric structure via a unique structural motif.

 When the group created a variant P5, which could not form a dimer based on structural information, the conformation of P5 itself was destabilized, which reduced its ability to regulate the endoplasmic reticulum stress sensor. In addition, the regulation of the protein aggregation inhibitory function (molecular chaperone activity) of P5 by calcium was also reduced. These results, which indicate that the dimeric structure of P5 is important for its full function, have provided an important medical insight.

 These research results were published in the online breaking news edition of the Structure journal on April 14, 2021.

View the article here.