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To define the molecular basis of this virus\u2013host interaction, we determined the 2.7-\u212b 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 \u223c40\u00b0. 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\u2013Barr virus IL-10 homolog (ebvIL-10), whose structure is highly similar to hIL-10, exhibits a \u223c20-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.<\/jats:p>","DOI":"10.1073\/pnas.152147499","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T22:26:28Z","timestamp":1027895188000},"page":"9404-9409","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":113,"title":["Crystal structure of human cytomegalovirus IL-10 bound to soluble human IL-10R1"],"prefix":"10.1073","volume":"99","author":[{"given":"Brandi C.","family":"Jones","sequence":"first","affiliation":[{"name":"Center for Biophysical Sciences and Engineering, Department of Microbiology, University of Alabama, 1025 18th Street South, Birmingham, AL 35294; and Center for Comparative Medicine, University of California, County Road 98 and Hutchison Drive, Davis, CA 95616"}]},{"given":"Naomi 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