{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:30:58Z","timestamp":1790800258214,"version":"4.1.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"52","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,12,30]]},"abstract":"<jats:p>Human interleukin-18 (hIL-18) is a cytokine that plays an important role in inflammation and host defense against microbes. Its activity is regulated in vivo by a naturally occurring antagonist, the human IL-18-binding protein (IL-18BP). Functional homologs of human IL-18BP are encoded by all orthopoxviruses, including variola virus, the causative agent of smallpox. They contribute to virulence by suppressing IL-18-mediated immune responses. Here, we describe the 2.0-\u212b resolution crystal structure of an orthopoxvirus IL-18BP, ectromelia virus IL-18BP (ectvIL-18BP), in complex with hIL-18. The hIL-18 structure in the complex shows significant conformational change at the binding interface compared with the structure of ligand-free hIL-18, indicating that the binding is mediated by an induced-fit mechanism. EctvIL-18BP adopts a canonical Ig fold and interacts via one edge of its \u03b2-sandwich with 3 cavities on the hIL-18 surface through extensive hydrophobic and hydrogen bonding interactions. Most of the ectvIL-18BP residues that participate in these interactions are conserved in both human and viral homologs, explaining their functional equivalence despite limited sequence homology. EctvIL-18BP blocks a putative receptor-binding site on IL-18, thus preventing IL-18 from engaging its receptor. Our structure provides insights into how IL-18BPs modulate hIL-18 activity. The revealed binding interface provides the basis for rational design of inhibitors against orthopoxvirus IL-18BP (for treating orthopoxvirus infection) or hIL-18 (for treating certain inflammatory and autoimmune diseases).<\/jats:p>","DOI":"10.1073\/pnas.0809086106","type":"journal-article","created":{"date-parts":[[2008,12,22]],"date-time":"2008-12-22T21:10:18Z","timestamp":1229980218000},"page":"20711-20715","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":74,"title":["Structural basis for antagonism of human interleukin 18 by poxvirus interleukin 18-binding protein"],"prefix":"10.1073","volume":"105","author":[{"given":"Brian","family":"Krumm","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangzhi","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junpeng","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,12,30]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/378088a0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.1999.0837"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80013-8"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.20.11537"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.6.3246"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.2217\/17460913.2.1.17"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2000.0689"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.3.1190"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.18.9960-9968.2003"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.10.5913"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.3.1164"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb993"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.2439"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.20.9947-9954.2001"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009581200"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.08.019"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2004.02.027"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/386190a0"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.2332\/allergolint.O-08-546"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071854"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.03.024"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709098105"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444903024491"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444906019949"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444994003112"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889807021206"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444996012255"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904019158"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444906005270"},{"key":"e_1_3_3_30_2","unstructured":"WL DeLano The PyMOL Molecular Graphics System.  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