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TitleStructure of endothelin ET receptor-G complex in a conformation stabilized by unique NPxxL motif.
Journal, issue, pagesCommun Biol, Vol. 7, Issue 1, Page 1303, Year 2024
Publish dateOct 16, 2024
AuthorsKazutoshi Tani / Saori Maki-Yonekura / Ryo Kanno / Tatsuki Negami / Tasuku Hamaguchi / Malgorzata Hall / Akira Mizoguchi / Bruno M Humbel / Tohru Terada / Koji Yonekura / Tomoko Doi /
PubMed AbstractEndothelin 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 ...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.
External linksCommun Biol / PubMed:39414992 / PubMed Central
MethodsEM (single particle)
Resolution3.21 - 4.6 Å
Structure data

38740

8xwp

EMDB-38740, PDB-8xwp:
Cryo-EM structure of ET-1 bound ETBR-DNGI complex
Method: EM (single particle) / Resolution: 3.21 Å

38741

8xwq

EMDB-38741, PDB-8xwq:
Cryo-EM structure of ET-1 bound ETBR-DNGI complex
Method: EM (single particle) / Resolution: 4.6 Å

60404

8zrt

EMDB-60404, PDB-8zrt:
Cryo-EM structure focused on the receptor of the ET-1 bound ETBR-DNGI complex
Method: EM (single particle) / Resolution: 3.62 Å

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
KeywordsMEMBRANE PROTEIN / ENDOTHELIN / RECEPTOR / Gi / COMPLEX

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