7SK7
Cryo-EM structure of human ACKR3 in complex with CXCL12, a small molecule partial agonist CCX662, and an extracellular Fab
Summary for 7SK7
| Entry DOI | 10.2210/pdb7sk7/pdb |
| EMDB information | 25175 |
| Descriptor | Atypical chemokine receptor 3, Stromal cell-derived factor 1, CID25 Fab light chain, ... (7 entities in total) |
| Functional Keywords | atypical chemokine receptor, membrane protein, signaling protein, signaling protein-immune system complex, signaling protein/immune system |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 116485.37 |
| Authors | Yen, Y.C.,Schafer, C.T.,Gustavsson, M.,Handel, T.M.,Tesmer, J.J.G. (deposition date: 2021-10-19, release date: 2022-07-27, Last modification date: 2024-11-20) |
| Primary citation | Yen, Y.C.,Schafer, C.T.,Gustavsson, M.,Eberle, S.A.,Dominik, P.K.,Deneka, D.,Zhang, P.,Schall, T.J.,Kossiakoff, A.A.,Tesmer, J.J.G.,Handel, T.M. Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias. Sci Adv, 8:eabn8063-eabn8063, 2022 Cited by PubMed Abstract: Both CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are activated by the chemokine CXCL12 yet evoke distinct cellular responses. CXCR4 is a canonical G protein-coupled receptor (GPCR), whereas ACKR3 is intrinsically biased for arrestin. The molecular basis for this difference is not understood. Here, we describe cryo-EM structures of ACKR3 in complex with CXCL12, a more potent CXCL12 variant, and a small-molecule agonist. The bound chemokines adopt an unexpected pose relative to those established for CXCR4 and observed in other receptor-chemokine complexes. Along with functional studies, these structures provide insight into the ligand-binding promiscuity of ACKR3, why it fails to couple to G proteins, and its bias toward β-arrestin. The results lay the groundwork for understanding the physiological interplay of ACKR3 with other GPCRs. PubMed: 35857509DOI: 10.1126/sciadv.abn8063 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.3 Å) |
Structure validation
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