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PDBsum entry 4oi8
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Transport protein,signaling protein/DNA
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PDB id
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4oi8
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DOI no:
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J Exp Med
210:2447-2463
(2013)
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PubMed id:
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RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA.
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C.M.Sirois,
T.Jin,
A.L.Miller,
D.Bertheloot,
H.Nakamura,
G.L.Horvath,
A.Mian,
J.Jiang,
J.Schrum,
L.Bossaller,
K.Pelka,
N.Garbi,
Y.Brewah,
J.Tian,
C.Chang,
P.S.Chowdhury,
G.P.Sims,
R.Kolbeck,
A.J.Coyle,
A.A.Humbles,
T.S.Xiao,
E.Latz.
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ABSTRACT
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Recognition of DNA and RNA molecules derived from pathogens or self-antigen is
one way the mammalian immune system senses infection and tissue damage.
Activation of immune signaling receptors by nucleic acids is controlled by
limiting the access of DNA and RNA to intracellular receptors, but the
mechanisms by which endosome-resident receptors encounter nucleic acids from the
extracellular space are largely undefined. In this study, we show that the
receptor for advanced glycation end-products (RAGE) promoted DNA uptake into
endosomes and lowered the immune recognition threshold for the activation of
Toll-like receptor 9, the principal DNA-recognizing transmembrane signaling
receptor. Structural analysis of RAGE-DNA complexes indicated that DNA
interacted with dimers of the outermost RAGE extracellular domains, and could
induce formation of higher-order receptor complexes. Furthermore, mice deficient
in RAGE were unable to mount a typical inflammatory response to DNA in the lung,
indicating that RAGE is important for the detection of nucleic acids in vivo.
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');
}
}
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