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Using a novel genetic complementation system involving the transduction of immortalized macrophages from genetically unresponsive C3H\/HeJ mice, we now have shown that the species-dependent discrimination between intact LPS and tetra-acyl LPS partial structures is fully attributable to the species origin of Toll-like receptor 4 (Tlr4), an essential membrane-spanning component of the mammalian LPS sensor. Because Tlr4 interprets the chemical structure of an LPS molecule, we conclude that LPS must achieve close physical proximity with Tlr4 in the course of signal transduction.<\/jats:p>","DOI":"10.1073\/pnas.040565397","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:38:21Z","timestamp":1027694301000},"page":"2163-2167","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":321,"title":["Physical contact between lipopolysaccharide and Toll-like receptor 4 revealed by genetic complementation"],"prefix":"10.1073","volume":"97","author":[{"given":"A.","family":"Poltorak","sequence":"first","affiliation":[{"name":"The Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9050; and Department of Biotechnology and Bioscience, Pz. della Scienza 2, 20126 Milan, 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