8XWV
Structure of CXCR2 bound to CXCL1 (CXCR2-CXCL1-Go Full map)
Summary for 8XWV
| Entry DOI | 10.2210/pdb8xwv/pdb |
| EMDB information | 38743 |
| Descriptor | Growth-regulated alpha protein, C-X-C chemokine receptor type 2, Guanine nucleotide-binding protein G(o) subunit alpha, ... (6 entities in total) |
| Functional Keywords | gpcr, arrestin, signaling protein-immune system complex, signaling protein/immune system |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 7 |
| Total formula weight | 161513.47 |
| Authors | Sano, F.K.,Saha, S.,Sharma, S.,Ganguly, M.,Shihoya, W.,Nureki, O.,Shukla, A.K.,Banerjee, R. (deposition date: 2024-01-16, release date: 2025-01-22, Last modification date: 2025-04-09) |
| Primary citation | Saha, S.,Sano, F.K.,Sharma, S.,Ganguly, M.,Mishra, S.,Dalal, A.,Akasaka, H.,Kobayashi, T.A.,Zaidi, N.,Tiwari, D.,Roy, N.,Yadav, M.K.,Banerjee, N.,Saha, S.,Mohapatra, S.,Itoh, Y.,Chevigne, A.,Banerjee, R.,Shihoya, W.,Nureki, O.,Shukla, A.K. Molecular basis of promiscuous chemokine binding and structural mimicry at the C-X-C chemokine receptor, CXCR2. Mol.Cell, 85:976-988.e9, 2025 Cited by PubMed Abstract: Selectivity of natural agonists for their cognate receptors is a hallmark of G-protein-coupled receptors (GPCRs); however, this selectivity often breaks down at the chemokine receptors. Chemokines often display promiscuous binding to chemokine receptors, but the underlying molecular determinants remain mostly elusive. Here, we perform a comprehensive transducer-coupling analysis, testing all known C-X-C chemokines on every C-X-C type chemokine receptor to generate a global fingerprint of the selectivity and promiscuity encoded within this system. Taking lead from this, we determine cryoelectron microscopy (cryo-EM) structures of the most promiscuous receptor, C-X-C chemokine receptor 2 (CXCR2), in complex with several chemokines. These structural snapshots elucidate the details of ligand-receptor interactions, including structural motifs, which are validated using mutagenesis and functional experiments. We also observe that most chemokines position themselves on CXCR2 as a dimer while CXCL6 exhibits a monomeric binding pose. Taken together, our findings provide the molecular basis of chemokine promiscuity at CXCR2 with potential implications for developing therapeutic molecules. PubMed: 39978339DOI: 10.1016/j.molcel.2025.01.024 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.07 Å) |
Structure validation
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