Crystal structure of human cytomegalovirus IL-10 bound to soluble human IL-10R1

Brandi C. Jones, Naomi J. Logsdon, Kristopher Josephson, Jennifer Cook, Peter A Barry, Mark R. Walter

Research output: Contribution to journalArticlepeer-review

110 Scopus citations


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-I0R2. To define the molecular basis of this virus-host interaction, we determined the 2.7-Å 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 ∼40°. 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 EpsteinBarr virus IL-10 homolog (ebvIL-10), whose structure is highly similar to hIL-10, exhibits a ∼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.

Original languageEnglish (US)
Pages (from-to)9404-9409
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number14
StatePublished - Jul 9 2002

ASJC Scopus subject areas

  • Genetics
  • General


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