6X93

Interleukin-10 signaling complex with IL-10RA and IL-10RB

Summary for 6X93

• Entry DOI: 10.2210/pdb6x93/pdb
• EMDB information: 22098
• Descriptor: Interleukin-10, Interleukin-10 receptor subunit alpha, Interleukin-10 receptor subunit beta (3 entities in total)
• Functional Keywords: il-10, cytokine, receptor, il-10ra, il-10rb, signaling
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 133540.54

Authors

Saxton, R.A.,Tsutsumi, N.,Gati, C.,Garcia, K.C. (deposition date: 2020-06-02, release date: 2021-03-17, Last modification date: 2024-10-16)

Primary citation

Saxton, R.A.,Tsutsumi, N.,Su, L.L.,Abhiraman, G.C.,Mohan, K.,Henneberg, L.T.,Aduri, N.G.,Gati, C.,Garcia, K.C.
Structure-based decoupling of the pro- and anti-inflammatory functions of interleukin-10.
Science, 371:-, 2021

PubMed Abstract: Interleukin-10 (IL-10) is an immunoregulatory cytokine with both anti-inflammatory and immunostimulatory properties and is frequently dysregulated in disease. We used a structure-based approach to deconvolute IL-10 pleiotropy by determining the structure of the IL-10 receptor (IL-10R) complex by cryo-electron microscopy at a resolution of 3.5 angstroms. The hexameric structure shows how IL-10 and IL-10Rα form a composite surface to engage the shared signaling receptor IL-10Rβ, enabling the design of partial agonists. IL-10 variants with a range of IL-10Rβ binding strengths uncovered substantial differences in response thresholds across immune cell populations, providing a means of manipulating IL-10 cell type selectivity. Some variants displayed myeloid-biased activity by suppressing macrophage activation without stimulating inflammatory CD8 T cells, thereby uncoupling the major opposing functions of IL-10. These results provide a mechanistic blueprint for tuning the pleiotropic actions of IL-10.

PubMed: 33737461
DOI: 10.1126/science.abc8433

Experimental method

ELECTRON MICROSCOPY (3.5 Å)