6v55
From Proteopedia
Full extracellular region of zebrafish Gpr126/Adgrg6
Structural highlights
FunctionAGRG6_DANRE G-protein coupled receptor which is activated by type IV collagen, a major constituent of the basement membrane. Couples to G(i)-proteins as well as G(s)-proteins (PubMed:25118328). Essential for normal differentiation of promyelinating Schwann cells and for normal myelination of axons (PubMed:19745155). Plays also a role in inner ear development (PubMed:24067352).[UniProtKB:Q86SQ4][1] [2] [3] Plays an important role in heart development (PubMed:24082093). Necessary and sufficient for axon sorting by Schwann cells independently of the ADGRG6-CTF (PubMed:25695270).[4] [5] Publication Abstract from PubMedMany drugs target the extracellular regions (ECRs) of cell-surface receptors. The large and alternatively-spliced ECRs of adhesion G protein-coupled receptors (aGPCRs) have key functions in diverse biological processes including neurodevelopment, embryogenesis, and tumorigenesis. However, their structures and mechanisms of action remain unclear, hampering drug development. The aGPCR Gpr126/Adgrg6 regulates Schwann cell myelination, ear canal formation, and heart development; and GPR126 mutations cause myelination defects in human. Here, we determine the structure of the complete zebrafish Gpr126 ECR and reveal five domains including a previously unknown domain. Strikingly, the Gpr126 ECR adopts a closed conformation that is stabilized by an alternatively spliced linker and a conserved calcium-binding site. Alternative splicing regulates ECR conformation and receptor signaling, while mutagenesis of the calcium-binding site abolishes Gpr126 function in vivo. These results demonstrate that Gpr126 ECR utilizes a multi-faceted dynamic approach to regulate receptor function and provide relevant insights for ECR-targeted drug design. Structural basis for adhesion G protein-coupled receptor Gpr126 function.,Leon K, Cunningham RL, Riback JA, Feldman E, Li J, Sosnick TR, Zhao M, Monk KR, Arac D Nat Commun. 2020 Jan 10;11(1):194. doi: 10.1038/s41467-019-14040-1. PMID:31924782[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
