Tsukuba, Japan—The human body is composed of approximately 60 trillion cells, which rely on the coordinated exchange of information to maintain normal biological functions. Each cell is surrounded by a membrane that facilitates the transmission of external signals into the cell through receptor proteins. Despite the clear elucidation of the binding structure of endothelin (ET), a vasoconstrictive peptide hormone, to the endothelin B-type receptor (ET B R) on the plasma membrane, the detailed structure of the ET B R-G protein complex—essential for signal transmission on the membrane—remains unclear. Additionally, the precise mechanism of signal transduction is not yet fully understood.
In this study, researchers utilized cryo-electron microscopy to observe the complex structure of ET, ET B R, and G protein. A strong binding interaction was revealed between the G protein and ET B R. The study also offered valuable insights into the mechanisms that distinguish types of G proteins and the factors that activate the receptor.
These findings may deepen our understanding of endothelin signaling mechanisms and have practical implications for the development of new drugs based on these structural properties.
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This research was partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research) from AMED under Grant Numbers JP21am0101118, JP21am0101116, JP22ama121006, JP23ama121004, and JP23ama121027, JST-Mirai Program Grant Number JPMJMI23G2. This work was supported by JSPS KAKENHI Grant Number 20H03210, ISHIZUE 2019 from the Kyoto University Research Development Program, and Center for Quantum and Information Life Sciences, University of Tsukuba.
Title of original paper:
Structure of endothelin ETB receptor-Gi complex in a conformation stabilized by unique NPxxL motif
Journal:
Communications Biology
DOI:
10.1038/s42003-024-06905-z
Professor TANI, Kazutoshi
Center for Computational Sciences, University of Tsukuba
Dr. Bruno M. Humbel
Provost Office, Okinawa Institute of Science and Technology Graduate University (OIST)
Professor TERADA, Tohru
Department of Biotechnology, Graduate School of Agricultural and Life Sciences, University of Tokyo
Group Director / Professor YONEKURA, Koji
RIKEN SPring-8 Center / Institute of Multidisciplinary Research for Advanced Materials, Tohoku University
Dr. DOI, Tomoko
Graduate School of Science, Kyoto University
Center for Computational Sciences
Communications Biology
Structure of endothelin ETB receptor–Gi complex in a conformation stabilized by unique NPxxL motif
16-Oct-2024