8YI7
The Cryo-EM structure of IL-12, receptor subunit beta-1 and receptor subunit beta-2 complex, local refinement
Summary for 8YI7
Entry DOI | 10.2210/pdb8yi7/pdb |
Related | 8XRP |
EMDB information | 38609 39311 |
Descriptor | Interleukin-12 subunit alpha, Interleukin-12 subunit beta, Interleukin-12 receptor subunit beta-2, ... (6 entities in total) |
Functional Keywords | il-12, il-12rb1, il-12rb2, receptor complex, cytokine |
Biological source | Homo sapiens (human) More |
Total number of polymer chains | 4 |
Total formula weight | 118764.21 |
Authors | Chen, H.Q.,Ge, X.F. (deposition date: 2024-02-29, release date: 2024-07-24, Last modification date: 2024-10-30) |
Primary citation | Chen, H.,Ge, X.,Li, C.,Zeng, J.,Wang, X. Structure and assembly of the human IL-12 signaling complex. Structure, 32:1640-, 2024 Cited by PubMed Abstract: Interleukin (IL)-12 is a heterodimeric pro-inflammatory cytokine. Our cryoelectron microscopy structure determination of human IL-12 in complex with IL-12Rβ1 and IL-12Rβ2 at a resolution of 3.75 Å reveals that IL-12Rβ2 primarily interacts with the IL-12p35 subunit via its N-terminal Ig-like domain, while IL-12Rβ1 binds to the p40 subunit with its N-terminal fibronectin III domain. This binding mode of IL-12 with its receptors is similar to that of IL-23 but shows notable differences with other cytokines. Through structural information and biochemical assays, we identified Y62, Y189, and K192 as key residues in IL-12p35, which bind to IL-12Rβ2 with high affinity and mediate IL-12 signal transduction. Furthermore, structural comparisons reveal two distinctive conformational states and structural plasticity of the heterodimeric interface in IL-12. As a result, our study advances our understanding of IL-12 signal initiation and opens up new opportunities for the engineering and therapeutic targeting of IL-12. PubMed: 39111304DOI: 10.1016/j.str.2024.07.010 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (3.57 Å) |
Structure validation
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