Presenter Profile
Yoshikazu Tanaka
Associate Professor
Tohoku University, Graduate School of Information Science
Yoshikazu Tanaka is an associate professor at Tohoku University's Applied Molecular Life Sciences laboratory. He holds a doctoral degree in Bioengineering from Tohoku University and has a keen interest in exploring molecular structures to understand various biological processes. With a background at esteemed institutions such as Hokkaido University and the Max Planck Institute, he conducts cutting-edge research in molecular life sciences. His current focus is on elucidating the mechanisms of life through molecular analyses.
TALK TITLE
Structure and functional analysis of a protein from marine natural products that activate cytokine receptors
KEYWORDS
Protein, X-ray crystallography, cytokine
ABSTRACT
Many drugs have been created by isolating and purifying substances produced by organisms in the natural environment and improving them. Our research group found thrombocorticin (ThC), a protein with a molecular weight of about 14 kDa that has similar activity to thrombopoietin, a hematopoietic cytokine (i.e., activation of thrombopoietin receptors), from a library of natural compounds derived from marine organisms. ThC binds to fucose and mannose and uses this activity to activate the thrombopoietin receptor signaling pathway. In this study, we characterized the molecular characteristics of ThC by biochemical experiments and structural analysis, and obtained insights into the activation mechanism of Mpl by ThC. The results of X-ray crystallography and cell biology showed that ThC induces intracellular signaling by binding to glycans on MPL and forcibly dimerizing MPL. Activation of MPL via cell surface sugar chains is associated with diseases such as myeloproliferative neoplasms. Therefore, the mechanism of signal activation via glycans revealed in this study may provide clues to these diseases.