| 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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