8YI7

The Cryo-EM structure of IL-12, receptor subunit beta-1 and receptor subunit beta-2 complex, local refinement

8YI7 の概要

• エントリーDOI: 10.2210/pdb8yi7/pdb
• 関連するPDBエントリー: 8XRP
• EMDBエントリー: 38609 39311
• 分子名称: Interleukin-12 subunit alpha, Interleukin-12 subunit beta, Interleukin-12 receptor subunit beta-2, ... (6 entities in total)
• 機能のキーワード: il-12, il-12rb1, il-12rb2, receptor complex, cytokine
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 118764.21

構造登録者

Chen, H.Q.,Ge, X.F. (登録日: 2024-02-29, 公開日: 2024-07-24, 最終更新日: 2024-11-20)

主引用文献

Chen, H.,Ge, X.,Li, C.,Zeng, J.,Wang, X.
Structure and assembly of the human IL-12 signaling complex.
Structure, 32:1640-, 2024

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: 39111304
DOI: 10.1016/j.str.2024.07.010

実験手法

ELECTRON MICROSCOPY (3.57 Å)