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| | ==Crystal structure of the dimeric coiled-coil domain of the cytosolic nucleic acid sensor LRRFIP1== | | ==Crystal structure of the dimeric coiled-coil domain of the cytosolic nucleic acid sensor LRRFIP1== |
| - | <StructureSection load='4h22' size='340' side='right' caption='[[4h22]], [[Resolution|resolution]] 2.89Å' scene=''> | + | <StructureSection load='4h22' size='340' side='right'caption='[[4h22]], [[Resolution|resolution]] 2.89Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4h22]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H22 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4H22 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4h22]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H22 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2q6q|2q6q]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.89Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LRRFIP1, GCF2, TRIP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4h22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h22 OCA], [https://pdbe.org/4h22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h22 RCSB], [https://www.ebi.ac.uk/pdbsum/4h22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h22 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4h22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h22 OCA], [http://pdbe.org/4h22 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4h22 RCSB], [http://www.ebi.ac.uk/pdbsum/4h22 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4h22 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LRRF1_HUMAN LRRF1_HUMAN]] Transcriptional repressor which preferentially binds to the GC-rich consensus sequence (5'-AGCCCCCGGCG-3') and may regulate expression of TNF, EGFR and PDGFA. May control smooth muscle cells proliferation following artery injury through PDGFA repression. May also bind double-stranded RNA. Positively regulates Toll-like receptor (TLR) signaling in response to agonist probably by competing with the negative FLII regulator for MYD88-binding.<ref>PMID:10364563</ref> <ref>PMID:14522076</ref> <ref>PMID:16199883</ref> <ref>PMID:19265123</ref> <ref>PMID:9705290</ref> | + | [https://www.uniprot.org/uniprot/LRRF1_HUMAN LRRF1_HUMAN] Transcriptional repressor which preferentially binds to the GC-rich consensus sequence (5'-AGCCCCCGGCG-3') and may regulate expression of TNF, EGFR and PDGFA. May control smooth muscle cells proliferation following artery injury through PDGFA repression. May also bind double-stranded RNA. Positively regulates Toll-like receptor (TLR) signaling in response to agonist probably by competing with the negative FLII regulator for MYD88-binding.<ref>PMID:10364563</ref> <ref>PMID:14522076</ref> <ref>PMID:16199883</ref> <ref>PMID:19265123</ref> <ref>PMID:9705290</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Modis, Y]] | + | [[Category: Large Structures]] |
| - | [[Category: Nguyen, J B]] | + | [[Category: Modis Y]] |
| - | [[Category: Flightless-1]] | + | [[Category: Nguyen JB]] |
| - | [[Category: Nucleic acid sensor]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Function
LRRF1_HUMAN Transcriptional repressor which preferentially binds to the GC-rich consensus sequence (5'-AGCCCCCGGCG-3') and may regulate expression of TNF, EGFR and PDGFA. May control smooth muscle cells proliferation following artery injury through PDGFA repression. May also bind double-stranded RNA. Positively regulates Toll-like receptor (TLR) signaling in response to agonist probably by competing with the negative FLII regulator for MYD88-binding.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
LRRFIP1 binds cytoplasmic double-stranded DNA and RNA and interacts with FLI, the mammalian homolog of Drosophila flightless I, through a highly conserved 87-amino acid domain. Upon binding nucleic acid ligands, LRRFIP1 recruits and activates beta-catenin, leading to the IRF3-dependent production of type I interferon. However, the molecular mechanism of LRRFIP1 signaling is not well understood. Here we show that the FLI-interacting domain of LRRFIP1 forms a classic parallel, homodimeric coiled coil with 10 heptad repeats and 22 helical turns. The coiled coil domain is also a dimer in solution. However, a longer LRRFIP1 construct spanning the coiled coil and DNA binding domains assembles into higher order oligomers in solution. The structure of LRRFIP1-CC constitutes a valuable tool for probing the mechanism of LRRFIP1 signaling and for structural studies of larger LRRFIP1 constructs.
Crystal structure of the dimeric coiled-coil domain of the cytosolic nucleic acid sensor LRRFIP1.,Nguyen JB, Modis Y J Struct Biol. 2012 Oct 23. pii: S1047-8477(12)00274-2. doi:, 10.1016/j.jsb.2012.10.006. PMID:23099021[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Khachigian LM, Santiago FS, Rafty LA, Chan OL, Delbridge GJ, Bobik A, Collins T, Johnson AC. GC factor 2 represses platelet-derived growth factor A-chain gene transcription and is itself induced by arterial injury. Circ Res. 1999 Jun 11;84(11):1258-67. PMID:10364563
- ↑ Rikiyama T, Curtis J, Oikawa M, Zimonjic DB, Popescu N, Murphy BA, Wilson MA, Johnson AC. GCF2: expression and molecular analysis of repression. Biochim Biophys Acta. 2003 Oct 1;1629(1-3):15-25. PMID:14522076
- ↑ Suriano AR, Sanford AN, Kim N, Oh M, Kennedy S, Henderson MJ, Dietzmann K, Sullivan KE. GCF2/LRRFIP1 represses tumor necrosis factor alpha expression. Mol Cell Biol. 2005 Oct;25(20):9073-81. PMID:16199883 doi:http://dx.doi.org/25/20/9073
- ↑ Dai P, Jeong SY, Yu Y, Leng T, Wu W, Xie L, Chen X. Modulation of TLR signaling by multiple MyD88-interacting partners including leucine-rich repeat Fli-I-interacting proteins. J Immunol. 2009 Mar 15;182(6):3450-60. doi: 10.4049/jimmunol.0802260. PMID:19265123 doi:http://dx.doi.org/10.4049/jimmunol.0802260
- ↑ Reed AL, Yamazaki H, Kaufman JD, Rubinstein Y, Murphy B, Johnson AC. Molecular cloning and characterization of a transcription regulator with homology to GC-binding factor. J Biol Chem. 1998 Aug 21;273(34):21594-602. PMID:9705290
- ↑ Nguyen JB, Modis Y. Crystal structure of the dimeric coiled-coil domain of the cytosolic nucleic acid sensor LRRFIP1. J Struct Biol. 2012 Oct 23. pii: S1047-8477(12)00274-2. doi:, 10.1016/j.jsb.2012.10.006. PMID:23099021 doi:http://dx.doi.org/10.1016/j.jsb.2012.10.006
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