4oi7 | pdb_00004oi7
RAGE recognizes nucleic acids and promotes inflammatory responses to DNA
Structural highlights
FunctionRAGE_HUMAN Mediates interactions of advanced glycosylation end products (AGE). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. Acts as a mediator of both acute and chronic vascular inflammation in conditions such as atherosclerosis and in particular as a complication of diabetes. AGE/RAGE signaling plays an important role in regulating the production/expression of TNF-alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. Interaction with S100A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Receptor for amyloid beta peptide. Contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular space in cortical neurons. ABPP-initiated RAGE signaling, especially stimulation of p38 mitogen-activated protein kinase (MAPK), has the capacity to drive a transport system delivering ABPP as a complex with RAGE to the intraneuronal space.[1] Publication Abstract from PubMedRecognition 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. RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA.,Sirois CM, Jin T, Miller AL, Bertheloot D, Nakamura H, Horvath GL, Mian A, Jiang J, Schrum J, Bossaller L, Pelka K, Garbi N, Brewah Y, Tian J, Chang C, Chowdhury PS, Sims GP, Kolbeck R, Coyle AJ, Humbles AA, Xiao TS, Latz E J Exp Med. 2013 Oct 21;210(11):2447-63. doi: 10.1084/jem.20120201. Epub 2013 Sep , 30. PMID:24081950[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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