Physical contact between lipopolysaccharide and toll-like receptor 4 revealed by genetic complementation

A Poltorak, P Ricciardi-Castagnoli… - Proceedings of the …, 2000 - National Acad Sciences
A Poltorak, P Ricciardi-Castagnoli, S Citterio, B Beutler
Proceedings of the National Academy of Sciences, 2000National Acad Sciences
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 …
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.
National Acad Sciences