8iy5 | pdb_00008iy5
ETB-Gi complex bound to endothelin-1
Structural highlights
FunctionGNAI1_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.[1] [2] Publication Abstract from PubMedThe endothelin ET(B) receptor is a promiscuous G-protein coupled receptor that is activated by vasoactive peptide endothelins. ET(B) signaling induces reactive astrocytes in the brain and vasorelaxation in vascular smooth muscle. Consequently, ET(B) agonists are expected to be drugs for neuroprotection and improved anti-tumor drug delivery. Here, we report the cryo-electron microscopy structure of the endothelin-1-ET(B)-G(i) complex at 2.8 A resolution, with complex assembly stabilized by a newly established method. Comparisons with the inactive ET(B) receptor structures revealed how endothelin-1 activates the ET(B) receptor. The NPxxY motif, essential for G-protein activation, is not conserved in ET(B), resulting in a unique structural change upon G-protein activation. Compared with other GPCR-G-protein complexes, ET(B) binds G(i) in the shallowest position, further expanding the diversity of G-protein binding modes. This structural information will facilitate the elucidation of G-protein activation and the rational design of ET(B) agonists. Cryo-EM structure of the endothelin-1-ET(B)-G(i) complex.,Sano FK, Akasaka H, Shihoya W, Nureki O Elife. 2023 Apr 25;12:e85821. doi: 10.7554/eLife.85821. PMID:37096326[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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