1LQS

CRYSTAL STRUCTURE OF HUMAN CYTOMEGALOVIRUS IL-10 BOUND TO SOLUBLE HUMAN IL-10R1

Summary for 1LQS

• Entry DOI: 10.2210/pdb1lqs/pdb
• Related: 1J7V
• Descriptor: INTERLEUKIN-10 RECEPTOR ALPHA CHAIN, INTERLEUKIN-10-LIKE PROTEIN, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: interleukin 10, helix bundle, receptor complex, molecular recognition, structure mimic, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 85738.81

Authors

Jones, B.C.,Logsdon, N.J.,Josephson, K.,Cook, J.,Barry, P.A.,Walter, M.R. (deposition date: 2002-05-13, release date: 2002-07-17, Last modification date: 2024-11-06)

Primary citation

Jones, B.C.,Logsdon, N.J.,Josephson, K.,Cook, J.,Barry, P.A.,Walter, M.R.
Crystal structure of human cytomegalovirus IL-10 bound to soluble human IL-10R1.
Proc.Natl.Acad.Sci.USA, 99:9404-9409, 2002

PubMed Abstract: Human IL-10 (hIL-10) modulates critical immune and inflammatory responses by way of interactions with its high- (IL-10R1) and low-affinity (IL-10R2) cell surface receptors. Human cytomegalovirus exploits the IL-10 signaling pathway by expressing a functional viral IL-10 homolog (cmvIL-10), which shares only 27% sequence identity with hIL-10 yet signals through IL-10R1 and IL-10R2. To define the molecular basis of this virus-host interaction, we determined the 2.7-A crystal structure of cmvIL-10 bound to the extracellular fragment of IL-10R1 (sIL-10R1). The structure reveals cmvIL-10 forms a disulfide-linked homodimer that binds two sIL-10R1 molecules. Although cmvIL-10 and hIL-10 share similar intertwined topologies and sIL-10R1 binding sites, their respective interdomain angles differ by approximately 40 degrees. This difference results in a striking re-organization of the IL-10R1s in the putative cell surface complex. Solution binding studies show cmvIL-10 and hIL-10 share essentially identical affinities for sIL-10R1 whereas the Epstein-Barr virus IL-10 homolog (ebvIL-10), whose structure is highly similar to hIL-10, exhibits a approximately 20-fold reduction in sIL-10R1 affinity. Our results suggest cmvIL-10 and ebvIL-10 have evolved different molecular mechanisms to engage the IL-10 receptors that ultimately enhance the respective ability of their virus to escape immune detection.

PubMed: 12093920
DOI: 10.1073/pnas.152147499

Experimental method

X-RAY DIFFRACTION (2.7 Å)