TY - JOUR
T1 - Physical contact between lipopolysaccharide and toll-like receptor 4 revealed by genetic complementation
AU - Poltorak, A.
AU - Ricciardi-Castagnoli, P.
AU - Citterio, S.
AU - Beutler, B.
PY - 2000/2/29
Y1 - 2000/2/29
N2 - Some mammalian species show an ability to discriminate between different lipopolysaccharide (LPS) partial structures (for example, lipid A and its congener LA-14-PP, which lacks secondary acyl chains), whereas others do not. 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.
AB - Some mammalian species show an ability to discriminate between different lipopolysaccharide (LPS) partial structures (for example, lipid A and its congener LA-14-PP, which lacks secondary acyl chains), whereas others do not. 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.
KW - C3H/HeJ
KW - Endotoxin
KW - Macrophage
KW - Specificity
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U2 - 10.1073/pnas.040565397
DO - 10.1073/pnas.040565397
M3 - Article
C2 - 10681462
AN - SCOPUS:0034007076
SN - 0027-8424
VL - 97
SP - 2163
EP - 2167
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 5
ER -