1lqs
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Human IL-10 (hIL-10) modulates critical immune and inflammatory responses | + | 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. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Human herpesvirus 5]] | [[Category: Human herpesvirus 5]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Barry, P | + | [[Category: Barry, P A.]] |
[[Category: Cook, J.]] | [[Category: Cook, J.]] | ||
| - | [[Category: Jones, B | + | [[Category: Jones, B C.]] |
[[Category: Josephson, K.]] | [[Category: Josephson, K.]] | ||
| - | [[Category: Logsdon, N | + | [[Category: Logsdon, N J.]] |
| - | [[Category: Walter, M | + | [[Category: Walter, M R.]] |
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: helix bundle]] | [[Category: helix bundle]] | ||
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[[Category: structure mimic]] | [[Category: structure mimic]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:47:31 2008'' |
Revision as of 11:47, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN CYTOMEGALOVIRUS IL-10 BOUND TO SOLUBLE HUMAN IL-10R1
Overview
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.
About this Structure
1LQS is a Protein complex structure of sequences from Homo sapiens and Human herpesvirus 5 with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of human cytomegalovirus IL-10 bound to soluble human IL-10R1., Jones BC, Logsdon NJ, Josephson K, Cook J, Barry PA, Walter MR, Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9404-9. Epub 2002 Jul 1. PMID:12093920
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