Biochemical and functional analysis of TIR domain containing protein from Brucella melitensis.
Toll/interleukin-1 like receptors are evolutionarily conserved proteins in eukaryotes that play crucial role in pathogen recognition and innate immune responses. Brucella are facultative intracellular bacterial pathogens causing brucellosis in animal and human hosts. Brucella behave as a stealthy pathogen by evading the immune recognition or suppressing the TLR signaling cascades. Brucella encode a TIR domain containing protein, TcpB, which suppresses NF-kappaB activation as well as pro-inflammatory cytokine secretion mediated by TLR2 and TLR4 receptors. TcpB targets the TIRAP mediated pathway to suppress TLR signaling. With the objective of detailed characterization, we have over expressed and purified TcpB from Brucella melitensis in native condition. The purified protein exhibited lipid-binding properties and cell permeability. NF-kappaB inhibition property of endogenous TcpB has also been demonstrated. The data provide insight into the mechanism of action of TcpB in the intracellular niche of Brucella.
Radhakrishnan
Girish K
GK
Department of Pathobiological Sciences, University of Wisconsin-Madison, WI, USA.
Splitter
Gary A
GA
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017347:Brucella melitensis / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D058619:Maltose-Binding Proteins; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D033902:Periplasmic Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D001426:Bacterial Proteins; D058619:Maltose-Binding Proteins; D016328:NF-kappa B; D033902:Periplasmic Binding Proteins; D010716:Phosphatidylinositols; D011993:Recombinant Fusion Proteins; C587630:TcpB protein, Brucella melitensis; D037521:Virulence Factors
J Immunol. 2010 Jan 15;184(2):956-64
20018612
Vet Microbiol. 2002 Dec 20;90(1-4):281-97
12414149
J Biol Chem. 2009 Apr 10;284(15):9892-8
19196716
PLoS Pathog. 2008 Feb 8;4(2):e21
18266466
Curr Top Microbiol Immunol. 2006;311:1-16
17048703
Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1673-8
15632218
DNA Cell Biol. 2002 Dec;21(12):879-94
12573048
Infect Dis Clin North Am. 1994 Mar;8(1):225-41
8021445
Nat Rev Immunol. 2008 Dec;8(12):911-22
18989317
Annu Rev Immunol. 2003;21:335-76
12524386
J Mol Recognit. 2003 Sep-Oct;16(5):265-71
14523939
Infect Immun. 2006 Jan;74(1):594-601
16369016
N Engl J Med. 2005 Jun 2;352(22):2325-36
15930423
PLoS One. 2007 Jul 18;2(7):e631
17637846
Nat Immunol. 2001 Aug;2(8):675-80
11477402
Nat Rev Immunol. 2007 May;7(5):353-64
17457343
Trends Microbiol. 2003 May;11(5):215-9
12781524
Nature. 2000 Nov 2;408(6808):111-5
11081518
Crit Rev Immunol. 2000;20(5):393-405
11145217
Cell Res. 2010 Jan;20(1):24-33
19997086
Adv Exp Med Biol. 2005;560:11-8
15932016
J Leukoc Biol. 2006 Aug;80(2):220-6
16698941
J Biotechnol. 2007 May 1;129(3):555-64
17331607
Infect Immun. 2000 Jul;68(7):4255-63
10858243
Nat Med. 2008 Apr;14(4):399-406
18327267
Infect Immun. 1998 Dec;66(12):5711-24
9826346