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Although most CXCR6 mutants examined were expressed at levels similar to wild\u2010type (WT) CXCR6, an N\u2010terminal E3Q mutant was poorly expressed, which may explain previously reported protective effects of a similar single nucleotide polymorphism, with respect to late\u2010stage HIV\u20101 infection. In contrast to several other chemokine receptors, mutation of the CXCR6 N\u2004terminus and inhibition of post\u2010translational modifications of this region were without effect on receptor function. Likewise, N\u2010terminal extension of CXCL16 resulted in a protein with decent potency and efficacy in chemotaxis and not, as anticipated, a CXCR6 antagonist. D176N and E274Q CXCR6 mutants were unable to interact with soluble CXCL16, suggesting a critical role for D176 and E274 in ligand binding. Intriguingly, although unable to interact with soluble CXCL16, the E274Q mutant could promote robust adhesion to membrane\u2010anchored CXCL16, suggesting that soluble and membrane\u2010bound forms of CXCL16 possess distinct conformations. Collectively, our data suggest a novel paradigm for the CXCR6:CXCL16 interaction, a finding which may impact the discovery of small\u2010molecule antagonists of CXCR6.<\/jats:p>","DOI":"10.1002\/eji.200838269","type":"journal-article","created":{"date-parts":[[2008,7,16]],"date-time":"2008-07-16T06:52:22Z","timestamp":1216191142000},"page":"2337-2350","source":"Crossref","is-referenced-by-count":24,"title":["Site\u2010directed mutagenesis of the chemokine receptor CXCR6 suggests a novel paradigm for interactions with the ligand CXCL16"],"prefix":"10.1002","volume":"38","author":[{"given":"Sarah\u2004J.","family":"Petit","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi\u2004E.","family":"Chayen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James\u2004E.","family":"Pease","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,7,24]]},"reference":[{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra052723"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/79738"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.8.5145"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.6.3678"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.10.6362"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000761200"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.4.1647"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/hq1001.096652"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000114565.42679.c6"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1003465"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.32.19084"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.32.19972"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205684200"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205685200"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400163200"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80577-2"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.11.1661"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201396200"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00556-06"},{"key":"e_1_2_8_20_2","doi-asserted-by":"crossref","first-page":"19271","DOI":"10.1016\/S0021-9258(19)47297-9","article-title":"Inhibition of mucin glycosylation by aryl\u2010N\u2010acetyl\u2010alpha\u2010galactosaminides in human colon cancer cells.","volume":"264","author":"Kuan S. 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