8ODX
Interleukin 12 receptor subunit beta-1 Fn domains in complex with antagonistic FAb4 fragment and VHH.
Summary for 8ODX
| Entry DOI | 10.2210/pdb8odx/pdb |
| Related | 8C7M 8CR5 8CR6 8CR8 |
| Descriptor | Interleukin-12 receptor subunit beta-1, FAb4 Heavy chain, anti Kappa Light chain VHH, ... (4 entities in total) |
| Functional Keywords | receptor, fibronectin, antagonist, cytokine |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 110923.17 |
| Authors | Bloch, Y.,Savvides, S.N. (deposition date: 2023-03-09, release date: 2024-02-07, Last modification date: 2024-11-13) |
| Primary citation | Bloch, Y.,Felix, J.,Merceron, R.,Provost, M.,Symakani, R.A.,De Backer, R.,Lambert, E.,Mehdipour, A.R.,Savvides, S.N. Structures of complete extracellular receptor assemblies mediated by IL-12 and IL-23. Nat.Struct.Mol.Biol., 31:591-597, 2024 Cited by PubMed Abstract: Cell-surface receptor complexes mediated by pro-inflammatory interleukin (IL)-12 and IL-23, both validated therapeutic targets, are incompletely understood due to the lack of structural insights into their complete extracellular assemblies. Furthermore, there is a paucity of structural details describing the IL-12-receptor interaction interfaces, in contrast to IL-23-receptor complexes. Here we report structures of fully assembled mouse IL-12/human IL-23-receptor complexes comprising the complete extracellular segments of the cognate receptors determined by electron cryo-microscopy. The structures reveal key commonalities but also surprisingly diverse features. Most notably, whereas IL-12 and IL-23 both utilize a conspicuously presented aromatic residue on their α-subunit as a hotspot to interact with the N-terminal Ig domain of their high-affinity receptors, only IL-12 juxtaposes receptor domains proximal to the cell membrane. Collectively, our findings will help to complete our understanding of cytokine-mediated assemblies of tall cytokine receptors and will enable a cytokine-specific interrogation of IL-12/IL-23 signaling in physiology and disease. PubMed: 38287195DOI: 10.1038/s41594-023-01190-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (4.4 Å) |
Structure validation
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