6V55
Full extracellular region of zebrafish Gpr126/Adgrg6
Summary for 6V55
| Entry DOI | 10.2210/pdb6v55/pdb |
| Descriptor | Adhesion G-protein coupled receptor G6, CALCIUM ION, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | adhesion g-protein coupled receptor, myelination, calcium-binding, cell adhesion |
| Biological source | Danio rerio (Zebrafish) More |
| Total number of polymer chains | 2 |
| Total formula weight | 90258.61 |
| Authors | |
| Primary citation | Leon, K.,Cunningham, R.L.,Riback, J.A.,Feldman, E.,Li, J.,Sosnick, T.R.,Zhao, M.,Monk, K.R.,Arac, D. Structural basis for adhesion G protein-coupled receptor Gpr126 function. Nat Commun, 11:194-194, 2020 Cited by PubMed Abstract: Many 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. PubMed: 31924782DOI: 10.1038/s41467-019-14040-1 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.38 Å) |
Structure validation
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