8ZRT

Cryo-EM structure focused on the receptor of the ET-1 bound ETBR-DNGI complex

Summary for 8ZRT

• Entry DOI: 10.2210/pdb8zrt/pdb
• EMDB information: 60404
• Descriptor: Endothelin receptor type B, Endothelin-1 (2 entities in total)
• Functional Keywords: endothelin, receptor, gi, complex, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 41306.21

Authors

Tani, K.,Maki-Yonekura, S.,Kanno, R.,Negami, T.,Hamaguchi, T.,Hall, M.,Mizoguchi, A.,Humbel, B.M.,Terada, T.,Yonekura, K.,Doi, T. (deposition date: 2024-06-05, release date: 2024-10-02, Last modification date: 2024-10-30)

Primary citation

Tani, K.,Maki-Yonekura, S.,Kanno, R.,Negami, T.,Hamaguchi, T.,Hall, M.,Mizoguchi, A.,Humbel, B.M.,Terada, T.,Yonekura, K.,Doi, T.
Structure of endothelin ET B receptor-G i complex in a conformation stabilized by unique NPxxL motif.
Commun Biol, 7:1303-1303, 2024

PubMed Abstract: Endothelin type B receptor (ETR) plays a crucial role in regulating blood pressure and humoral homeostasis, making it an important therapeutic target for related diseases. ETR activation by the endogenous peptide hormones endothelin (ET)-1-3 stimulates several signaling pathways, including G, G, G, G, and β-arrestin. Although the conserved NPxxY motif in transmembrane helix 7 (TM7) is important during GPCR activation, ETR possesses the lesser known NPxxL motif. In this study, we present the cryo-EM structure of the ETR-G complex, complemented by MD simulations and functional studies. These investigations reveal an unusual movement of TM7 to the intracellular side during ETR activation and the essential roles of the diverse NPxxL motif in stabilizing the active conformation of ETR and organizing the assembly of the binding pocket for the α5 helix of G protein. These findings enhance our understanding of the interactions between GPCRs and G proteins, thereby advancing the development of therapeutic strategies.

PubMed: 39414992
DOI: 10.1038/s42003-024-06905-z

Experimental method

ELECTRON MICROSCOPY (3.62 Å)