5T5W

Structure of an affinity matured lambda-IFN/IFN-lambdaR1/IL-10Rbeta receptor complex

5T5W の概要

• エントリーDOI: 10.2210/pdb5t5w/pdb
• 分子名称: Interleukin-10 receptor subunit beta, Interferon lambda receptor 1, Interferon lambda-3, ... (5 entities in total)
• 機能のキーワード: receptor, cytokine, cytokine-cytokine receptor complex, cytokine/cytokine receptor
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 70324.78

構造登録者

Mendoza, J.L.,Jude, K.M.,Garcia, K.C. (登録日: 2016-08-31, 公開日: 2017-03-29, 最終更新日: 2024-10-23)

主引用文献

Mendoza, J.L.,Schneider, W.M.,Hoffmann, H.H.,Vercauteren, K.,Jude, K.M.,Xiong, A.,Moraga, I.,Horton, T.M.,Glenn, J.S.,de Jong, Y.P.,Rice, C.M.,Garcia, K.C.
The IFN-lambda-IFN-lambda R1-IL-10R beta Complex Reveals Structural Features Underlying Type III IFN Functional Plasticity.
Immunity, 46:379-392, 2017

PubMed Abstract: Type III interferons (IFN-λs) signal through a heterodimeric receptor complex composed of the IFN-λR1 subunit, specific for IFN-λs, and interleukin-10Rβ (IL-10Rβ), which is shared by multiple cytokines in the IL-10 superfamily. Low affinity of IL-10Rβ for cytokines has impeded efforts aimed at crystallizing cytokine-receptor complexes. We used yeast surface display to engineer a higher-affinity IFN-λ variant, H11, which enabled crystallization of the ternary complex. The structure revealed that IL-10Rβ uses a network of tyrosine residues as hydrophobic anchor points to engage IL-10 family cytokines that present complementary hydrophobic binding patches, explaining its role as both a cross-reactive but cytokine-specific receptor. H11 elicited increased anti-proliferative and antiviral activities in vitro and in vivo. In contrast, engineered higher-affinity type I IFNs did not increase antiviral potency over wild-type type I IFNs. Our findings provide insight into cytokine recognition by the IL-10R family and highlight the plasticity of type III interferon signaling and its therapeutic potential.

PubMed: 28329704
DOI: 10.1016/j.immuni.2017.02.017

実験手法

X-RAY DIFFRACTION (2.847 Å)