9QXL
The structure of ADGRL4 in the active-state
Summary for 9QXL
| Entry DOI | 10.2210/pdb9qxl/pdb |
| EMDB information | 53437 |
| Descriptor | Green fluorescent protein,Adhesion G protein-coupled receptor L4, GNAS complex locus,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (4 entities in total) |
| Functional Keywords | adhesion gpcr, adgrl4, eltd1, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 146976.72 |
| Authors | Chen, Q.,Favara, D.M. (deposition date: 2025-04-15, release date: 2026-01-14, Last modification date: 2026-02-18) |
| Primary citation | Chen, Q.,Gusach, A.,Diamante, A.,Patel, J.C.,Edwards, P.C.,Tate, C.G.,Favara, D.M. Structure of the G q -coupled adhesion receptor ADGRL4. Nat Commun, 17:907-907, 2025 Cited by PubMed Abstract: Adhesion G protein-coupled receptors (aGPCRs) are a 32-member family of Class B GPCRs that have diverse cellular roles including mechanosensation, cell-fate determination, neurodevelopment, immune function and tumour biology. ADGRL4 is upregulated in the tumour microenvironment and is implicated in tumour pathogenesis across a broad range of malignancies. Inhibiting ADGRL4 is a potential therapeutic treatment for currently intractable cancers such as glioblastoma. Previous work suggested that ADGRL4 does not signal through G protein coupled pathways. However, using a sensitive bioluminescent assay, we demonstrate here that ADGRL4 couples weakly to the heterotrimeric G protein G, whilst there is no robust coupling to other G proteins (G, G, G) or β-arrestin 1 or 2. We determine the cryo-EM structure of ADGRL4 coupled to a heterotrimeric G complex to a resolution of 3.1 Å. The overall fold of ADGRL4 is similar to that of other aGPCRs, but the coupling to G is distinct with fewer interactions between the receptor and G protein. The structure is consistent with ADGRL4 being activated by its tethered agonist and represents an important step towards the development of potential inhibitors for the treatment of multiple tumour types. PubMed: 41469374DOI: 10.1038/s41467-025-67629-0 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.14 Å) |
Structure validation
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